Semiconductor source based near infrared measurement device with improved signal-to-noise ratio

ABSTRACT

A measurement system is provided with a light source that is configured to increase signal-to-noise ratio by increasing a light intensity from at least one of a plurality of semiconductor sources. An apparatus to receive a portion of the output optical beam, and deliver an analysis output beam to a sample. A receiver to: receive and process at least a portion of the analysis output beam reflected or transmitted from the sample, generate an output signal, and synchronize to the light source. A smart phone or tablet to: receive and process at least a portion of the output signal, store and display the processed output signal, and transmit at least a portion of the processed output signal. A cloud to: receive an output status comprising the at least a portion of the processed output signal, process the received output status to generate processed data, and store the processed data.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. application Ser. No.16/284,514 filed Feb. 25, 2019, which is a Continuation of U.S.application Ser. No. 16/016,649 filed Jun. 24, 2018 (now U.S. Pat. No.10,213,113), which is a Continuation of U.S. application Ser. No.15/860,065 filed Jan. 2, 2018 (now U.S. Pat. No. 10,098,546), which is aContinuation of U.S. application Ser. No. 15/686,198 filed Aug. 25, 2017(now U.S. Pat. No. 9,861,286), which is a Continuation of U.S.application Ser. No. 15/357,136 filed Nov. 21, 2016 (now U.S. Pat. No.9,757,040), which is a Continuation of U.S. application Ser. No.14/651,367 filed Jun. 11, 2015 (now U.S. Pat. No. 9,500,635), which isthe U.S. national phase of PCT Application No. PCT/US2013/075736 filedDec. 17, 2013, which claims the benefit of U.S. provisional applicationSer. No. 61/747,477 filed Dec. 31, 2012 and U.S. provisional applicationSer. No. 61/754,698 filed Jan. 21, 2013, the disclosures of which arehereby incorporated by reference in their entirety.

This application is also a continuation of U.S. application Ser. No.16/506,885 filed Jul. 9, 2019, which is a continuation of U.S.application Ser. No. 16/272,069 filed Feb. 11, 2019, which is acontinuation of U.S. application Ser. No. 16/029,611 filed Jul. 8, 2018(now U.S. Pat. No. 10,201,283), which is a continuation of U.S.application Ser. No. 15/888,052 filed Feb. 4, 2018 (now U.S. Pat. No.10,136,819), which is a continuation of U.S. application Ser. No.15/212,549 filed Jul. 18, 2016 (now U.S. Pat. No. 9,885,698), which is acontinuation of U.S. application Ser. No. 14/650,897 filed Jun. 10, 2015(now U.S. Pat. No. 9,494,567), which is a U.S. National Phase ofPCT/US2013/075700 filed Dec. 17, 2013, which claims the benefit of U.S.provisional application Ser. No. 61/747,472 filed Dec. 31, 2012, thedisclosures of all of which are hereby incorporated in their entirety byreference herein.

U.S. application Ser. No. 16/506,885 is also a continuation of U.S.application Ser. No. 16/004,359 filed Jun. 9, 2018, which is acontinuation of U.S. application Ser. No. 14/109,007 filed Dec. 17, 2013(now U.S. Pat. No. 9,993,159), which claims the benefit of U.S.provisional application Ser. No. 61/747,553 filed Dec. 31, 2012, thedisclosures of all of which are hereby incorporated in their entirety byreference herein.

U.S. application Ser. No. 16/506,885 is also a continuation of U.S.application Ser. No. 16/188,194 filed Nov. 12, 2018 (now U.S. Pat. No.10,386,230), which is a continuation of U.S. application Ser. No.16/004,154 filed Jun. 8, 2018 (now U.S. Pat. No. 10,126,283), which is acontinuation of U.S. application Ser. No. 15/855,201 filed Dec. 27, 2017(now U.S. Pat. No. 9,995,722), which is a continuation of U.S.application Ser. No. 15/711,907 filed Sep. 21, 2017 (now U.S. Pat. No.9,897,584), which is a divisional of U.S. application Ser. No.15/357,225 filed Nov. 21, 2016 (now U.S. Pat. No. 9,797,876), which is acontinuation of U.S. application Ser. No. 14/650,981 filed Jun. 10, 2015(now U.S. Pat. No. 9,500,634), which is the U.S. national phase of PCTApplication No. PCT/US2013/075767 filed Dec. 17, 2013, which claims thebenefit of U.S. provisional application Ser. No. 61/747,485 filed Dec.31, 2012, the disclosures of all of which are hereby incorporated byreference in their entirety.

U.S. application Ser. No. 16/506,885 is also a continuation of U.S.application Ser. No. 16/241,628 filed Jan. 7, 2019 (now U.S. Pat. No.10,441,176), which is a continuation of U.S. Ser. No. 16/015,737 filedJun. 22, 2018 (now U.S. Pat. No. 10,172,523), which is a continuation ofU.S. Ser. No. 15/594,053 filed May 12, 2017 (now U.S. Pat. No.10,188,299), which is a continuation of U.S. application Ser. No.14/875,709 filed Oct. 6, 2015 (now U.S. Pat. No. 9,651,533), which is acontinuation of U.S. application Ser. No. 14/108,986 filed Dec. 17, 2013(now U.S. Pat. No. 9,164,032), which claims the benefit of U.S.provisional application Ser. No. 61/747,487 filed Dec. 31, 2012, thedisclosures of all of which are hereby incorporated in their entirety byreference herein.

U.S. application Ser. No. 16/506,885 is also a continuation of U.S.application Ser. No. 16/284,514 filed Feb. 25, 2019, which is acontinuation of U.S. application Ser. No. 16/016,649 filed Jun. 24, 2018(now U.S. Pat. No. 10,213,113), which is a continuation of U.S.application Ser. No. 15/860,065 filed Jan. 2, 2018 (now U.S. Pat. No.10,098,546), which is a Continuation of U.S. application Ser. No.15/686,198 filed Aug. 25, 2017 (now U.S. Pat. No. 9,861,286), which is acontinuation of U.S. application Ser. No. 15/357,136 filed Nov. 21, 2016(now U.S. Pat. No. 9,757,040), which is a continuation of U.S.application Ser. No. 14/651,367 filed Jun. 11, 2015 (now U.S. Pat. No.9,500,635), which is the U.S. national phase of PCT Application No.PCT/US2013/075736 filed Dec. 17, 2013, which claims the benefit of U.S.provisional application Ser. No. 61/747,477 filed Dec. 31, 2012 and U.S.provisional application Ser. No. 61/754,698 filed Jan. 21, 2013, thedisclosures of all of which are hereby incorporated by reference intheir entirety.

This application is related to U.S. provisional application Ser. No.61/747,472 filed Dec. 31, 2012; Ser. No. 61/747,481 filed Dec. 31, 2012;Ser. No. 61/747,485 filed Dec. 31, 2012; Ser. No. 61/747,487 filed Dec.31, 2012; Ser. No. 61/747,492 filed Dec. 31, 2012; and Ser. No.61/747,553 filed Dec. 31, 2012, the disclosures of which are herebyincorporated by reference in their entirety herein.

This application has a common priority date with commonly owned U.S.application Ser. No. 14/650,897 filed Jun. 10, 2015 (now U.S. Pat. No.9,494,567), which is the U.S. national phase of InternationalApplication PCT/US2013/075700 entitled Near-Infrared Lasers ForNon-Invasive Monitoring Of Glucose, Ketones, HBAlC, And Other BloodConstituents; U.S. application Ser. No. 14/108,995 filed Dec. 17, 2013(published as US 2014/0188092) entitled Focused Near-Infrared Lasers ForNon-Invasive Vasectomy And Other Thermal Coagulation Or OcclusionProcedures; U.S. application Ser. No. 14/650,981 filed Jun. 10, 2015(now U.S. Pat. No. 9,500,634), which is the U.S. national phase ofInternational Application PCT/US2013/075767 entitled Short-Wave InfraredSuper-Continuum Lasers For Natural Gas Leak Detection, Exploration, AndOther Active Remote Sensing Applications; U.S. application Ser. No.14/108,986 filed Dec. 17, 2013 (now U.S. Pat. No. 9,164,032) entitledShort-Wave Infrared Super-Continuum Lasers For Detecting Counterfeit OrIllicit Drugs And Pharmaceutical Process Control; U.S. application Ser.No. 14/108,974 filed Dec. 17, 2013 (Published as US2014/0188094)entitled Non-Invasive Treatment Of Varicose Veins; and U.S. applicationSer. No. 14/109,007 filed Dec. 17, 2013 (Published as US2014/0236021)entitled Near-Infrared Super-Continuum Lasers For Early Detection OfBreast And Other Cancers, the disclosures of all of which are herebyincorporated in their entirety by reference herein.

TECHNICAL FIELD

This disclosure relates to lasers and light sources for healthcare,medical, dental, or bio-technology applications, including systems andmethods for using near-infrared or short-wave infrared light sources forearly detection of dental caries, often called cavities.

BACKGROUND AND SUMMARY

Dental care and the prevention of dental decay or dental caries haschanged in the United States over the past several decades, due to theintroduction of fluoride to drinking water, the use of fluoridedentifrices and rinses, application of topical fluoride in the dentaloffice, and improved dental hygiene. Despite these advances, dentaldecay continues to be the leading cause of tooth loss. With theimprovements over the past several decades, the majority of newlydiscovered carious lesions tend to be localized to the occlusal pits andfissures of the posterior dentition and the proximal contact sites.These early carious lesions may be often obscured in the complex andconvoluted topography of the pits and fissures or may be concealed bydebris that frequently accumulates in those regions of the posteriorteeth. Moreover, such lesions are difficult to detect in the earlystages of development.

Dental caries may be a dynamic disease that is characterized by toothdemineralization leading to an increase in the porosity of the enamelsurface. Leaving these lesions untreated may potentially lead tocavities reaching the dentine and pulp and perhaps eventually causingtooth loss. Occlusal surfaces (bite surfaces) and approximal surfaces(between the teeth) are among the most susceptible sites ofdemineralization due to acid attack from bacterial by-products in thebiofilm. Therefore, there is a need for detection of lesions at an earlystage, so that preventive agents may be used to inhibit or reverse thedemineralization.

Traditional methods for caries detection include visual examination andtactile probing with a sharp dental exploration tool, often assisted byradiographic (x-ray) imaging. However, detection using these methods maybe somewhat subjective; and, by the time that caries are evident undervisual and tactile examination, the disease may have already progressedto an advanced stage. Also, because of the ionizing nature of x-rays,they are dangerous to use (limited use with adults, and even less usedwith children). Although x-ray methods are suitable for approximalsurface lesion detection, they offer reduced utility for screening earlycaries in occlusal surfaces due to their lack of sensitivity at veryearly stages of the disease.

Some of the current imaging methods are based on the observation of thechanges of the light transport within the tooth, namely absorption,scattering, transmission, reflection and/or fluorescence of light.Porous media may scatter light more than uniform media. Taking advantageof this effect, the Fiber-optic trans-illumination is a qualitativemethod used to highlight the lesions within teeth by observing thepatterns formed when white light, pumped from one side of the tooth, isscattered away and/or absorbed by the lesion. This technique may bedifficult to quantify due to an uneven light distribution inside thetooth.

Another method called quantitative light-induced fluorescence—QLF—relieson different fluorescence from solid teeth and caries regions whenexcited with bright light in the visible. For example, when excited byrelatively high intensity blue light, healthy tooth enamel yields ahigher intensity of fluorescence than does demineralized enamel that hasbeen damaged by caries infection or any other cause. On the other hand,for excitation by relatively high intensity of red light, the oppositemagnitude change occurs, since this is the region of the spectrum forwhich bacteria and bacterial by-products in carious regions absorb andfluoresce more pronouncedly than do healthy areas. However, the imageprovided by QLF may be difficult to assess due to relatively poorcontrast between healthy and infected areas. Moreover, QLF may havedifficulty discriminating between white spots and stains because bothproduce similar effects. Stains on teeth are commonly observed in theocclusal sites of teeth, and this obscures the detection of caries usingvisible light.

As described in this disclosure, the near-infrared region of thespectrum offers a novel approach to imaging carious regions becausescattering is reduced and absorption by stains is low. For example, ithas been demonstrated that the scattering by enamel tissues reduces inthe form of 1/(wavelength)³, e.g., inversely as the cube of wavelength.By using a broadband light source in the short-wave infrared (SWIR) partof the spectrum, which corresponds approximately to 1400 nm to 2500 nm,lesions in the enamel and dentine may be observed. In one embodiment,intact teeth have low reflection over the SWIR wavelength range. In thepresence of caries, the scattering increases, and the scattering is afunction of wavelength; hence, the reflected signal decreases withincreasing wavelength. Moreover, particularly when caries exist in thedentine region, water build up may occur, and dips in the SWIR spectrumcorresponding to the water absorption lines may be observed. Thescattering and water absorption as a function of wavelength may thus beused for early detection of caries and for quantifying the degree ofdemineralization.

SWIR light may be generated by light sources such as lamps, lightemitting diodes, one or more laser diodes, super-luminescent laserdiodes, and fiber-based super-continuum sources. The SWIRsuper-continuum light sources advantageously may produce high intensityand power, as well as being a nearly transform-limited beam that mayalso be modulated. Also, apparatuses for caries detection may includeC-clamps over teeth, a handheld device with light input and lightdetection, which may also be attached to other dental equipment such asdrills. Alternatively, a mouth-guard type apparatus may be used tosimultaneously illuminate one or more teeth. Fiber optics may beconveniently used to guide the light to the patient as well as totransport the signal back to one or more detectors and receivers.

One approach to non-invasive monitoring of blood constituents or bloodanalytes is to use near-infrared spectroscopy, such as absorptionspectroscopy or near-infrared diffuse reflection or transmissionspectroscopy. Some attempts have been made to use broadband lightsources, such as tungsten lamps, to perform the spectroscopy. However,several challenges have arisen in these efforts. First, many otherconstituents in the blood also have signatures in the near-infrared, sospectroscopy and pattern matching, often called spectral fingerprinting,is required to distinguish the glucose with sufficient confidence.Second, the non-invasive procedures have often transmitted or reflectedlight through the skin, but skin has many spectral artifacts in thenear-infrared that may mask the glucose signatures. Moreover, the skinmay have significant water and blood content. These difficulties becomeparticularly complicated when a weak light source is used, such as alamp. More light intensity can help to increase the signal levels, and,hence, the signal-to-noise ratio.

In one embodiment, a wearable device includes a measurement deviceincluding a light source comprising a plurality of light emitting diodes(LEDs) for measuring one or more physiological parameters, themeasurement device configured to generate, by modulating at least one ofthe LEDs having an initial light intensity, an optical beam having aplurality of optical wavelengths, wherein at least a portion of theplurality of optical wavelengths is a near-infrared wavelength between700 nanometers and 2500 nanometers. The measurement device comprises oneor more lenses configured to receive and to deliver a portion of theoptical beam to tissue, wherein the tissue reflects at least a portionof the optical beam delivered to the tissue, and wherein the measurementdevice is adapted to be placed on a wrist or an ear of a user. Themeasurement device further comprises a receiver, the receiver having aplurality of spatially separated detectors and one or more analog todigital converters coupled to the spatially separated detectors, the oneor more analog to digital converters configured to generate at least tworeceiver outputs. The measurement device is configured to improve asignal-to-noise ratio of the optical beam reflected from the tissue bycomparing the at least two receiver outputs. The measurement device isalso configured to further improve the signal-to-noise ratio of theoptical beam reflected from the tissue by increasing the light intensityrelative to the initial light intensity from at least one of the LEDs.The measurement device is further configured to generate an outputsignal representing at least in part a non-invasive measurement on bloodcontained within the tissue. The receiver further comprises one or morespectral filters positioned in front of at least some of the pluralityof spatially separated detectors, wherein the receiver is configured tobe synchronized to the modulation of the at least one of the LED, andwherein the modulating at least one of the LEDs has a modulationfrequency, and wherein the receiver is configured to use a lock-intechnique that detects the modulation frequency.

In one or more embodiments, a wearable device comprises a measurementdevice including a light source comprising a plurality of light emittingdiodes (LEDs) for measuring one or more physiological parameters, themeasurement device configured to generate, by modulating at least one ofthe LEDs having an initial light intensity, an optical beam having aplurality of optical wavelengths, wherein at least a portion of theplurality of optical wavelengths is a near-infrared wavelength between700 nanometers and 2500 nanometers. The measurement device comprises oneor more lenses configured to receive and to deliver a portion of theoptical beam to tissue, wherein the tissue reflects at least a portionof the optical beam delivered to the tissue, and wherein the measurementdevice is adapted to be placed on a wrist or an ear of a user. Themeasurement device is configured to generate an output signalrepresenting at least in part a non-invasive measurement on bloodcontained within the tissue. The measurement device is configured toimprove a signal-to-noise ratio of the optical beam reflected from thetissue by increasing the light intensity relative to the initial lightintensity from at least one of the LEDs. The measurement device furthercomprises a receiver having one or more detectors, wherein one of theone or more detectors is located a first distance from a first one ofthe LEDs and a different distance from a second one of the LEDs suchthat the receiver can compare light received from the first LED andlight received from the second LED, and wherein the output signal isgenerated in part by comparing signals associated with the lightreceived from the first and second LEDs. The receiver is configured tobe synchronized to the modulation of the at least one of the LEDs,wherein the modulating at least one of the LEDs has a modulationfrequency, and wherein the receiver is configured to use a lock-intechnique that detects the modulation frequency.

In at least one embodiment, a wearable device comprises a measurementdevice including a light source comprising a plurality of light emittingdiodes (LEDs) for measuring one or more physiological parameters, themeasurement device configured to generate, by modulating at least one ofthe LEDs having an initial light intensity, an optical beam having aplurality of optical wavelengths, wherein at least a portion of theplurality of optical wavelengths is a near-infrared wavelength between700 nanometers and 2500 nanometers. The measurement device comprises oneor more lenses configured to receive and to deliver a portion of theoptical beam to tissue, wherein the tissue reflects at least a portionof the optical beam delivered to the tissue, and wherein the measurementdevice is adapted to be placed on a wrist or an ear of a user. Themeasurement device is further configured to generate an output signalrepresenting at least in part a non-invasive measurement on bloodcontained within the tissue. The measurement device is configured toimprove a signal-to-noise ratio of the optical beam reflected from thetissue by increasing the light intensity relative to the initial lightintensity from at least one of the LEDs. The measurement device furthercomprises a receiver, the receiver having a plurality of spatiallyseparated detectors configured to generate at least two receiveroutputs, and the measurement device configured to further improve thesignal-to-noise ratio of the optical beam reflected from the tissue bycomparing the at least two receiver outputs. One of the plurality ofdetectors is located a first distance from a first one of the LEDs and adifferent distance from a second one of the LEDs such that the receivercan generate a third signal responsive to light received from the firstLED and a fourth signal responsive to light received from the secondLED, and wherein the output signal is generated in part by comparing thethird and fourth signals, wherein the receiver is configured to besynchronized to the modulation of the at least one of the LEDs, andwherein the modulating at least one of the LEDs has a modulationfrequency, and wherein the receiver is configured to use a lock-intechnique that detects the modulation frequency.

In one or more embodiments, a wearable device includes a measurementdevice having a light source comprising a plurality of light emittingdiodes (LEDs) for measuring one or more physiological parameters. Themeasurement device is configured to generate, by modulating at least oneof the LEDs having an initial light intensity, an optical beam having aplurality of optical wavelengths, wherein at least a portion of theoptical beam includes a near-infrared wavelength between 700 nanometersand 2500 nanometers. The measurement device comprises one or more lensesconfigured to receive and to deliver at least a portion of the opticalbeam to tissue, wherein the tissue reflects at least a portion of theoptical beam delivered to the tissue. The measurement device furthercomprises a receiver having a plurality of spatially separated detectorsand one or more analog to digital converters coupled to the spatiallyseparated detectors, the one or more analog to digital converters beingconfigured to generate at least two receiver outputs. The receiver isconfigured to capture light while the LEDs are off and convert thecaptured light into a first signal, and to capture light while at leastone of the LEDs is on and to convert the captured light into a secondsignal, the captured light including at least a portion of the opticalbeam reflected from the tissue. The measurement device is configured toimprove a signal-to-noise ratio of the optical beam reflected from thetissue by differencing the first signal and the second signal and bydifferencing the two receiver outputs. The measurement device isconfigured to further improve the signal-to-noise ratio of the opticalbeam reflected from the tissue by increasing the light intensityrelative to the initial light intensity from at least one of the LEDs.The measurement device is further configured to generate an outputsignal representing at least in part a non-invasive measurement on bloodcontained within the tissue.

Embodiments may include a wearable device comprising a measurementdevice including a light source comprising a plurality of light emittingdiodes (LEDs) for measuring one or more physiological parameters. Themeasurement device is configured to generate, by modulating at least oneof the LEDs having an initial light intensity, an optical beam having aplurality of optical wavelengths, wherein at least a portion of theplurality of optical wavelengths is a near-infrared wavelength between700 nanometers and 2500 nanometers. The measurement device comprises oneor more lenses configured to receive and to deliver a portion of theoptical beam to tissue, wherein the tissue reflects at least a portionof the optical beam delivered to the tissue, and wherein the measurementdevice is adapted to be placed on a wrist or an ear of a user. Themeasurement device further comprises a receiver having a plurality ofspatially separated detectors and one or more analog to digitalconverters coupled to the spatially separated detectors. The one or moreanalog to digital converters is configured to generate at least tworeceiver outputs. The receiver is configured to capture light while theLEDs are off and convert the captured light into a first signal, and tocapture light while at least one of the LEDs is on and convert thecaptured light into a second signal, the captured light including atleast a portion of the optical beam reflected from the tissue. Themeasurement device is configured to improve a signal-to-noise ratio ofthe optical beam reflected from the tissue by differencing the firstsignal and the second signal and by differencing the two receiveroutputs. The measurement device is also configured to further improvethe signal-to-noise ratio of the optical beam reflected from the tissueby increasing the light intensity relative to the initial lightintensity from at least one of the LEDs. The measurement device isfurther configured to generate an output signal representing at least inpart a non-invasive measurement on blood contained within the tissue.

In one or more embodiments, a wearable device comprises a measurementdevice including a light source comprising a plurality of light emittingdiodes (LEDs) for measuring one or more physiological parameters. Themeasurement device is configured to generate, by modulating at least oneof the LEDs having an initial light intensity, an optical beam having aplurality of optical wavelengths, wherein at least a portion of theplurality of optical wavelengths is a near-infrared wavelength between700 nanometers and 2500 nanometers. The measurement device comprises oneor more lenses configured to receive and to deliver a portion of theoptical beam to tissue, wherein the tissue reflects at least a portionof the optical beam delivered to the tissue, and wherein the measurementdevice is adapted to be placed on a wrist or an ear of a user. Themeasurement device further comprises a receiver having a plurality ofspatially separated detectors and one or more analog to digitalconverters coupled to the spatially separated detectors, the one or moreanalog to digital converters configured to generate at least tworeceiver outputs. The receiver is configured to capture light while theLEDs are off and convert the captured light into a first signal, and tocapture light while at least one of the LEDs is on and convert thecaptured light into a second signal, the captured light including atleast a portion of the optical beam reflected from the tissue. Themeasurement device is configured to improve a signal-to-noise ratio ofthe optical beam reflected from the tissue by differencing the firstsignal and the second signal and by differencing the two receiveroutputs. The measurement device is configured to further improve thesignal-to-noise ratio of the optical beam reflected from the tissue byincreasing the light intensity relative to the initial light intensityfrom at least one of the LEDs. The measurement device is furtherconfigured to generate an output signal representing at least in part anon-invasive measurement on blood contained within the tissue, whereinthe output signal is generated at least in part by using a Fouriertransform and mathematical manipulation of a signal resulting from thecaptured light. The receiver further comprises one or more spectralfilters positioned in front of at least some of the plurality ofspatially separated detectors.

In one embodiment a measurement system is provided with a light source,an apparatus, a receiver, a smart phone or tablet, and a remote device.The light source comprises a plurality of semiconductor sources that areconfigured to generate an output optical beam with one or more opticalwavelengths, the light source is configured to increase signal-to-noiseratio by increasing a light intensity from at least one of the pluralityof semiconductor sources. The apparatus is configured to: receive aportion of the output optical beam, and deliver an analysis output beamto a sample. The receiver is configured to: receive and process at leasta portion of the analysis output beam reflected or transmitted from thesample, generate an output signal, and synchronize to the light source.The smart phone or tablet comprises a wireless receiver, a wirelesstransmitter, a display, a microphone, a speaker, one or more buttons orknobs, a microprocessor and a touch screen. The smart phone or tablet isconfigured to: receive and process at least a portion of the outputsignal, store and display the processed output signal, and transmit atleast a portion of the processed output signal over a wirelesstransmission link. The remote device is configured to: receive, over thewireless transmission link, an output status comprising the at least aportion of the processed output signal, process the received outputstatus to generate processed data, and store the processed data.

In another embodiment a measurement system is provided with a wearablemeasurement device for measuring one or more physiological parameters,including a light source comprising a plurality of semiconductor sourcesthat are configured to generate an output optical beam with one or moreoptical wavelengths. The light source is configured to increasesignal-to-noise ratio by increasing a light intensity from at least oneof the plurality of semiconductor sources. The wearable measurementdevice is configured to receive a portion of the output optical beam andto deliver an analysis output beam to a sample. The wearable measurementdevice further comprises a receiver configured to receive and process atleast a portion of the analysis output beam reflected or transmittedfrom the sample and to generate an output signal, wherein the wearablemeasurement device receiver is configured to be synchronized to pulsesof the light source. The measurement system is also provided with asmart phone or tablet and a remote device. The smart phone or tabletcomprises a wireless receiver, a wireless transmitter, a display, amicrophone, a speaker, one or more buttons or knobs, a microprocessorand a touch screen. The smart phone or tablet is configured to receiveand process at least a portion of the output signal, to store anddisplay the processed output signal, and to transmit a portion of theprocessed output signal over a wireless transmission link. The remotedevice is configured to receive over the wireless transmission link anoutput status comprising the at least a portion of the processed outputsignal, to process the received output status to generate processed dataand to store the processed data. The remote device is capable of storinga history of at least a portion of the received output status over aspecified period of time.

In yet another embodiment a wearable device for use with a smart phoneor tablet is provided with a measurement device including a light sourcecomprising a plurality of semiconductor sources for measuring one ormore physiological parameters. The measurement device is configured to:generate, by modulating at least one of the semiconductor sources havingan initial light intensity, an input optical beam having one or moreoptical wavelengths, and receive and to deliver a portion of the inputoptical beam to tissue, wherein the tissue reflects at least a portionof the input optical beam delivered to the tissue. The measurementdevice further comprises a receiver that is configured to: capture lightwhile the semiconductor sources are off and convert the captured lightinto a first signal, and capture light while at least one of thesemiconductor sources is on and convert the captured light into a secondsignal, the captured light including at least a portion of the inputoptical beam reflected from the tissue; synchronize to the modulation ofthe at least one of the semiconductor sources. The measurement device isfurther configured to improve a signal-to-noise ratio of the inputoptical beam reflected from the tissue by: differencing the first signaland the second signal, and increasing the light intensity relative tothe initial light intensity from at least one of the semiconductorsources. The measurement device is further configured to generate anoutput signal representing at least in part a non-invasive measurementon blood contained within the tissue. The wearable device is configuredto communicate with the smart phone or tablet. The smart phone or tabletcomprises a wireless receiver, a wireless transmitter, a display, avoice input module, a speaker, and a touch screen. The smart phone ortablet is configured to: receive and to process at least a portion ofthe output signal, store and display the processed output signal, andtransmit at least a portion of the processed output signal over awireless transmission link.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the present disclosure, and forfurther features and advantages thereof, reference is now made to thefollowing description taken in conjunction with the accompanyingdrawings, in which:

FIG. 1 illustrates the structure of a tooth.

FIG. 2A shows the attenuation coefficient for dental enamel and waterversus wavelength from approximately 600 nm to 2600 nm.

FIG. 2B illustrates the absorption spectrum of intact enamel and dentinein the wavelength range of approximately 1.2 to 2.4 microns.

FIG. 3 shows the near infrared spectral reflectance over the wavelengthrange of approximately 800 nm to 2500 nm from an occlusal tooth surface.The black diamonds correspond to the reflectance from a sound, intacttooth section. The asterisks correspond to a tooth section with anenamel lesion. The circles correspond to a tooth section with a dentinelesion.

FIG. 4 illustrates a hand-held dental tool design of a human interfacethat may also be coupled with other dental tools.

FIG. 5A illustrates a clamp design of a human interface to cap over oneor more teeth and perform a non-invasive measurement for dental caries.

FIG. 5B shows a mouth guard design of a human interface to perform anon-invasive measurement for dental caries.

FIG. 6A illustrates the dorsal of a hand for performing a differentialmeasurement for measuring blood constituents or analytes.

FIG. 6B illustrates the dorsal of a foot for performing a differentialmeasurement for measuring blood constituents or analytes.

FIG. 7 illustrates a block diagram or building blocks for constructinghigh power laser diode assemblies.

FIG. 8 shows a platform architecture for different wavelength ranges foran all-fiber-integrated, high powered, super-continuum light source.

FIG. 9 illustrates one embodiment for a short-wave infraredsuper-continuum light source.

FIG. 10 shows the output spectrum from the SWIR SC laser of FIG. 9 whenabout 10 m length of fiber for SC generation is used. This fiber is asingle-mode, non-dispersion shifted fiber that is optimized foroperation near 1550 nm.

FIG. 11A illustrates a schematic of the experimental set-up formeasuring the diffuse reflectance spectroscopy using the SWIR-SC lightsource of FIGS. 9 and 10.

FIG. 11B shows exemplary reflectance from a sound enamel region, anenamel lesion region, and a dentine lesion region. The spectra arenormalized to have equal value near 2050 nm.

FIGS. 12A-B illustrate high power SWIR-SC lasers that may generate lightbetween approximately 1.4-1.8 microns (FIG. 12A) or approximately 2-2.5microns (FIG. 12B).

FIG. 12C shows a reflection-spectroscopy based stand-off detectionsystem having an SC laser source.

FIG. 12D shows one example of a dual-beam experimental set-up that maybe used to subtract out (or at least minimize the adverse effects of)light source fluctuations.

FIG. 13 schematically shows that the medical measurement device can bepart of a personal or body area network that communicates with anotherdevice (e.g., smart phone or tablet) that communicates with the cloud.The cloud may in turn communicate information with the user, dental orhealthcare providers, or other designated recipients.

FIG. 14A is a schematic diagram of the basic elements of an imagingspectrometer.

FIG. 14B illustrates one example of a typical imaging spectrometer usedin hyper-spectral imaging systems.

FIG. 15 illustrates a flowchart of a smart manufacturing process.

DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS

As required, detailed embodiments of the present disclosure aredisclosed herein; however, it is to be understood that the disclosedembodiments are merely exemplary of the disclosure that may be embodiedin various and alternative forms. The figures are not necessarily toscale; some features may be exaggerated or minimized to show details ofparticular components. Therefore, specific structural and functionaldetails disclosed herein are not to be interpreted as limiting, butmerely as a representative basis for teaching one skilled in the art tovariously employ the present disclosure.

Near-infrared (NIR) and SWIR light may be preferred for caries detectioncompared to visible light imaging because the NIR/SWIR wavelengthsgenerally have lower absorption by stains and deeper penetration intoteeth. Hence, NIR/SWIR light may provide a caries detection method thatcan be non-invasive, non-contact and relatively stain insensitive.Broadband light may provide further advantages because carious regionsmay demonstrate spectral signatures from water absorption and thewavelength dependence of porosity in the scattering of light.

The wavelength of light should be selected appropriately to achieve anon-invasive procedure. For example, the light should be able topenetrate deep enough to reach through the dermis and subcutaneous fatlayers to reach varicose veins. For example, the penetration depth maybe defined as the inverse of the absorption coefficient, although it mayalso be necessary to include the scattering for the calculation. Toachieve penetration deep enough to reach the varicose veins, wavelengthsmay correspond to local minima in water 501 and adipose 502 absorption,as well as potentially local minima in collagen 503 and elastin 504absorption. For example, wavelengths near approximately 1100 nm, 1310nm, or 1650 nm may be advantageous for non-invasive procedures. Moregenerally, wavelength ranges of approximately 900 nm to 1150 nm, 1280 nmto 1340 nm, or 1550 nm to 1680 nm may be advantageous for non-invasiveprocedures.

In general, the near-infrared region of the electromagnetic spectrumcovers between approximately 0.7 microns (700 nm) to about 2.5 microns(2500 nm). However, it may also be advantageous to use just theshort-wave infrared between approximately 1.4 microns (1400 nm) andabout 2.5 microns (2500 nm). One reason for preferring the SWIR over theentire NIR may be to operate in the so-called “eye safe” window, whichcorresponds to wavelengths longer than about 1400 nm. Therefore, for theremainder of the disclosure the SWIR will be used for illustrativepurposes. However, it should be clear that the discussion that followscould also apply to using the NIR wavelength range, or other wavelengthbands.

In particular, wavelengths in the eye safe window may not transmit downto the retina of the eye, and therefore, these wavelengths may be lesslikely to create permanent eye damage from inadvertent exposure. Thenear-infrared wavelengths have the potential to be dangerous, becausethe eye cannot see the wavelengths (as it can in the visible), yet theycan penetrate and cause damage to the eye. Even if a practitioner is notlooking directly at the laser beam, the practitioner's eyes may receivestray light from a reflection or scattering from some surface. Hence, itcan always be a good practice to use eye protection when working aroundlasers. Since wavelengths longer than about 1400 nm are substantiallynot transmitted to the retina or substantially absorbed in the retina,this wavelength range is known as the eye safe window. For wavelengthslonger than 1400 nm, in general only the cornea of the eye may receiveor absorb the light radiation.

FIG. 1 illustrates the structure of an exemplary cross-section of atooth 100. The tooth 100 has a top layer called the crown 101 and belowthat a root 102 that reaches well into the gum 106 and bone 108 of themouth. The exterior of the crown 101 is an enamel layer 103, and belowthe enamel is a layer of dentine 104 that sits atop a layer of cementum107. Below the dentine 104 is a pulp region 105, which comprises withinit blood vessels 109 and nerves 110. If the light can penetrate theenamel 103 and dentine 104, then the blood flow and blood constituentsmay be measured through the blood vessels in the dental pulp 105. Whilethe amount of blood flow in the capillaries of the dental pulp 105 maybe less than an artery or vein, the smaller blood flow could still beadvantageous for detecting or measuring blood constituents as comparedto detection through the skin if there is less interfering spectralfeatures from the tooth. Although the structure of a molar tooth isillustrated in FIG. 1, other types of teeth also have similar structure.For example, different types of teeth include molars, pre-molars, canineand incisor teeth.

As used throughout this document, the term “couple” and or “coupled”refers to any direct or indirect communication between two or moreelements, whether or not those elements are physically connected to oneanother. As used throughout this disclosure, the term “spectroscopy”means that a tissue or sample is inspected by comparing differentfeatures, such as wavelength (or frequency), spatial location,transmission, absorption, reflectivity, scattering, refractive index, oropacity. In one embodiment, “spectroscopy” may mean that the wavelengthof the light source is varied, and the transmission, absorption, orreflectivity of the tissue or sample is measured as a function ofwavelength. In another embodiment, “spectroscopy” may mean that thewavelength dependence of the transmission, absorption or reflectivity iscompared between different spatial locations on a tissue or sample. Asan illustration, the “spectroscopy” may be performed by varying thewavelength of the light source, or by using a broadband light source andanalyzing the signal using a spectrometer, wavemeter, or opticalspectrum analyzer.

As used throughout this disclosure, the term “fiber laser” refers to alaser or oscillator that has as an output light or an optical beam,wherein at least a part of the laser comprises an optical fiber. Forinstance, the fiber in the “fiber laser” may comprise one of or acombination of a single mode fiber, a multi-mode fiber, a mid-infraredfiber, a photonic crystal fiber, a doped fiber, a gain fiber, or, moregenerally, an approximately cylindrically shaped waveguide orlight-pipe. In one embodiment, the gain fiber may be doped with rareearth material, such as ytterbium, erbium, and/or thulium, for example.In another embodiment, the mid-infrared fiber may comprise one or acombination of fluoride fiber, ZBLAN fiber, chalcogenide fiber,tellurite fiber, or germanium doped fiber. In yet another embodiment,the single mode fiber may include standard single-mode fiber, dispersionshifted fiber, non-zero dispersion shifted fiber, high-nonlinearityfiber, and small core size fibers.

As used throughout this disclosure, the term “pump laser” refers to alaser or oscillator that has as an output light or an optical beam,wherein the output light or optical beam is coupled to a gain medium toexcite the gain medium, which in turn may amplify another input opticalsignal or beam. In one particular example, the gain medium may be adoped fiber, such as a fiber doped with ytterbium, erbium, and/orthulium. In one embodiment, the “pump laser” may be a fiber laser, asolid state laser, a laser involving a nonlinear crystal, an opticalparametric oscillator, a semiconductor laser, or a plurality ofsemiconductor lasers that may be multiplexed together. In anotherembodiment, the “pump laser” may be coupled to the gain medium by usinga fiber coupler, a dichroic mirror, a multiplexer, a wavelength divisionmultiplexer, a grating, or a fused fiber coupler.

As used throughout this document, the term “super-continuum” and or“supercontinuum” and or “SC” refers to a broadband light beam or outputthat comprises a plurality of wavelengths. In a particular example, theplurality of wavelengths may be adjacent to one-another, so that thespectrum of the light beam or output appears as a continuous band whenmeasured with a spectrometer. In one embodiment, the broadband lightbeam may have a bandwidth or at least 10 nm. In another embodiment, the“super-continuum” may be generated through nonlinear opticalinteractions in a medium, such as an optical fiber or nonlinear crystal.For example, the “super-continuum” may be generated through one or acombination of nonlinear activities such as four-wave mixing, the Ramaneffect, modulational instability, and self-phase modulation.

As used throughout this disclosure, the terms “optical light” and or“optical beam” and or “light beam” refer to photons or light transmittedto a particular location in space. The “optical light” and or “opticalbeam” and or “light beam” may be modulated or unmodulated, which alsomeans that they may or may not contain information. In one embodiment,the “optical light” and or “optical beam” and or “light beam” mayoriginate from a fiber, a fiber laser, a laser, a light emitting diode,a lamp, a pump laser, or a light source.

Transmission or Reflection Through Teeth

The transmission, absorption and reflection from teeth has been studiedin the near infrared, and, although there are some features, the enameland dentine appear to be fairly transparent in the near infrared(particularly SWIR wavelengths between about 1400 and 2500 nm). Forexample, the absorption or extinction ratio for light transmission hasbeen studied. FIG. 2A illustrates the attenuation coefficient 200 fordental enamel 201 (filled circles) and the absorption coefficient ofwater 202 (open circles) versus wavelength. Near-infrared light maypenetrate much further without scattering through all the tooth enamel,due to the reduced scattering coefficient in normal enamel. Scatteringin enamel may be fairly strong in the visible, but decreases asapproximately 1/(wavelength)³ [i.e., inverse of the cube of thewavelength] with increasing wavelength to a value of only 2-3 cm-1 at1310 nm and 1550 nm in the near infrared. Therefore, enamel may bevirtually transparent in the near infrared with optical attenuation 1-2orders of magnitude less than in the visible range.

As another example, FIG. 2B illustrates the absorption spectrum 250 ofintact enamel 251 (dashed line) and dentine 252 (solid line) in thewavelength range of approximately 1.2 to 2.4 microns. In the nearinfrared there are two absorption bands in the areas of about 1.5 and 2microns. The band with a peak around 1.57 microns may be attributed tothe overtone of valent vibration of water present in both enamel anddentine. In this band, the absorption is greater for dentine than forenamel, which may be related to the large water content in this tissue.In the region of 2 microns, dentine may have two absorption bands, andenamel one. The band with a maximum near 2.1 microns may belong to theovertone of vibration of PO hydroxyapatite groups, which is the mainsubstance of both enamel and dentine. Moreover, the band with a peaknear 1.96 microns in dentine may correspond to water absorption (dentinemay contain substantially higher water than enamel).

In addition to the absorption coefficient, the reflectance from intactteeth and teeth with dental caries (e.g., cavities) has been studied. Inone embodiment, FIG. 3 shows the near infrared spectral reflectance 300over the wavelength range of approximately 800 nm to 2500 nm from anocclusal (e.g., top) tooth surface 304. The curve with black diamonds301 corresponds to the reflectance from a sound, intact tooth section.The curve with asterisks (*) 302 corresponds to a tooth section with anenamel lesion. The curve with circles 303 corresponds to a tooth sectionwith a dentine lesion. Thus, when there is a lesion, more scatteringoccurs and there may be an increase in the reflected light.

For wavelengths shorter than approximately 1400 nm, the shapes of thespectra remain similar, but the amplitude of the reflection changes withlesions. Between approximately 1400 nm and 2500 nm, an intact tooth 301has low reflectance (e.g., high transmission), and the reflectanceappears to be more or less independent of wavelength. On the other hand,in the presence of lesions 302 and 303, there is increased scattering,and the scattering loss may be wavelength dependent. For example, thescattering loss may decrease as the inverse of some power of wavelength,such as 1/(wavelength)³—so, the scattering loss decreases with longerwavelengths. When there is a lesion in the dentine 303, more water canaccumulate in the area, so there is also increased water absorption. Forexample, the dips near 1450 nm and 1900 nm may correspond to waterabsorption, and the reflectance dips are particularly pronounced in thedentine lesion 303.

FIG. 3 may point to several novel techniques for early detection andquantification of carious regions. One method may be to use a relativelynarrow wavelength range (for example, from a laser diode orsuper-luminescent laser diode) in the wavelength window below 1400 nm.In one embodiment, wavelengths in the vicinity of 1310 nm may be used,which is a standard telecommunications wavelength where appropriatelight sources are available. Also, it may be advantageous to use asuper-luminescent laser diode rather than a laser diode, because thebroader bandwidth may avoid the production of laser speckle that canproduce interference patterns due to light's scattering after strikingirregular surfaces. As FIG. 3 shows, the amplitude of the reflectedlight (which may also be proportional to the inverse of thetransmission) may increase with dental caries. Hence, comparing thereflected light from a known intact region with a suspect region mayhelp identify carious regions. However, one difficulty with using arelatively narrow wavelength range and relying on amplitude changes maybe the calibration of the measurement. For example, the amplitude of thereflected light may depend on many factors, such as irregularities inthe dental surface, placement of the light source and detector, distanceof the measurement instrument from the tooth, etc.

In one embodiment, use of a plurality of wavelengths can help to bettercalibrate the dental caries measurement. For example, a plurality oflaser diodes or super-luminescent laser diodes may be used at differentcenter wavelengths. Alternately, a lamp or alternate broadband lightsource may be used followed by appropriate filters, which may be placedafter the light source or before the detectors. In one example,wavelengths near 1090 nm, 1440 nm and 1610 nm may be employed. Thereflection from the tooth 305 appears to reach a local maximum near 1090nm in the representative embodiment illustrated. Also, the reflectancenear 1440 nm 306 is higher for dental caries, with a distinct dipparticularly for dentine caries 303. Near 1610 nm 307, the reflection isalso higher for carious regions. By using a plurality of wavelengths,the values at different wavelengths may help quantify a caries score. Inone embodiment, the degree of enamel lesions may be proportional to theratio of the reflectance near 1610 nm divided by the reflectance near1090 nm. Also, the degree of dentine lesion may be proportional to thedifference between the reflectance near 1610 nm and 1440 nm, with thedifference then divided by the reflectance near 1090 nm. Although oneset of wavelengths has been described, other wavelengths may also beused and are intended to be covered by this disclosure.

In yet another embodiment, it may be further advantageous to use all ofsome fraction of the SWIR between approximately 1400 and 2500 nm. Forexample, a SWIR super-continuum light source could be used, or a lampsource could be used. On the receiver side, a spectrometer and/ordispersive element could be used to discriminate the variouswavelengths. As FIG. 3 shows, an intact tooth 301 has a relatively lowand featureless reflectance over the SWIR. On the other hand, with acarious region there is more scattering, so the reflectance 302,303increases in amplitude. Since the scattering is inversely proportionalto wavelength or some power of wavelength, the carious regionreflectance 302, 303 also decreases with increasing wavelength.Moreover, the carious region may contain more water, so there are dipsin the reflectance near the water absorption lines 306 and 308. Thedegree of caries or caries score may be quantified by the shape of thespectrum over the SWIR, taking ratios of different parts of thespectrum, or some combination of this and other spectral processingmethods.

Although several methods of early caries detection using spectralreflectance have been described, other techniques could also be used andare intended to be covered by this disclosure. For example,transmittance may be used rather than reflectance, or a combination ofthe two could be used. Moreover, the transmittance, reflectance and/orabsorbance could also be combined with other techniques, such asquantitative light-induced fluorescence or fiber-optictrans-illumination. Also, the SWIR could be advantageous, but otherparts of the infrared, near-infrared or visible wavelengths may also beused consistent with this disclosure.

One other benefit of the absorption, transmission or reflectance in thenear infrared and SWIR may be that stains and non-calcified plaque arenot visible in this wavelength range, enabling better discrimination ofdefects, cracks, and demineralized areas. For example, dental calculus,accumulated plaque, and organic stains and debris may interferesignificantly with visual diagnosis and fluorescence-based cariesdetection schemes in occlusal surfaces. In the case of usingquantitative light-induced fluorescence, such confounding factorstypically may need to be removed by prophylaxis (abrasive cleaning)before reliable measurements can be taken. Surface staining at visiblewavelengths may further complicate the problem, and it may be difficultto determine whether pits and fissures are simply stained ordemineralized. On the other hand, staining and pigmentation generallyinterfere less with NIR or SWIR imaging. For example, NIR and SWIR lightmay not be absorbed by melanin and porphyrins produced by bacteria andthose found in food dyes that accumulate in dental plaque and areresponsible for the pigmentation.

Human Interface for Measurement System

A number of different types of measurements may be used to image fordental caries, particularly early detection of dental caries. A basicfeature of the measurements may be that the optical properties aremeasured as a function of wavelength at a plurality of wavelengths. Asfurther described below, the light source may output a plurality ofwavelengths, or a continuous spectrum over a range of wavelengths. Inone embodiment, the light source may cover some or all of the wavelengthrange between approximately 1400 nm and 2500 nm. The signal may bereceived at a receiver, which may also comprise a spectrometer orfilters to discriminate between different wavelengths. The signal mayalso be received at a camera, which may also comprise filters or aspectrometer. In one embodiment, the spectral discrimination usingfilters or a spectrometer may be placed after the light source ratherthan at the receiver. The receiver usually comprises one or moredetectors (optical-to-electrical conversion element) and electricalcircuitry. The receiver may also be coupled to analog to digitalconverters, particularly if the signal is to be fed to a digital device.

Referring to FIG. 1, one or more light sources 111 may be used forillumination. In one embodiment, a transmission measurement may beperformed by directing the light source output 111 to the region nearthe interface between the gum 106 and dentine 104. In one embodiment,the light may be directed using a light guide or a fiber optic. Thelight may then propagate through the dental pulp 105 to the other side,where the light may be incident on one or more detectors or anotherlight guide to transport the signal to 112 a spectrometer, receiver,and/or camera, for example. In one embodiment, the light source may bedirected to one or more locations near the interface between the gum 106and dentine 104 (in one example, could be from the two sides of thetooth). The transmitted light may then be detected in the occlusalsurface above the tooth using a 112 spectrometer, receiver, or camera,for example. In another embodiment, a reflectance measurement may beconducted by directing the light source output 111 to, for example, theocclusal surface of the tooth, and then detecting the reflectance at a113 spectrometer, receiver or camera. Although a few embodiments forimaging the tooth are described, other embodiments and techniques mayalso be used and are intended to be covered by this disclosure. Theseoptical techniques may measure optical properties such as reflectance,transmittance, absorption, or luminescence.

In one embodiment, FIG. 4 shows that the light source and/or detectionsystem may be integrated with a dental hand-piece 400. The hand-piece400 may also include other dental equipment, such as a drill, pick, airspray or water cooling stream. The dental hand-piece 400 may include ahousing 401 and a motor housing 402 (in some embodiments such as with adrill, a motor may be placed in this section). The end of hand-piece 403that interfaces with the tooth may be detachable, and it may also havethe light input and output end. The dental hand-piece 400 may also havean umbilical cord 404 for connecting to power supplies, diagnostics, orother equipment, for example.

A light guide 405 may be integrated with the hand-piece 400, eitherinside the housing 401, 402 or adjacent to the housing. In oneembodiment, a light source 410 may be contained within the housing 401,402. In an alternative embodiment, the hand-piece 400 may have a coupler410 to couple to an external light source 411 and/or detection system orreceiver 412. The light source 411 may be coupled to the hand-piece 400using a light guide or fiber optic cable 406. In addition, the detectionsystem or receiver 412 may be coupled to the hand-piece 400 using one ormore light guides, fiber optic cable or a bundle of fibers 407.

The light incident on the tooth may exit the hand-piece 400 through theend 403. The end 403 may also have a lens system or curved mirror systemto collimate or focus the light. In one embodiment, if the light sourceis integrated with a tool such as a drill, then the light may reach thetooth at the same point as the tip of the drill. The reflected ortransmitted light from the tooth may then be observed externally and/orguided back through the light guide 405 in the hand-piece 400. Ifobserved externally, there may be a lens system 408 for collecting thelight and a detection system 409 that may have one or more detectors andelectronics. If the light is to be guided back through the hand-piece400, then the reflected light may transmit through the light guide 405back to the detection system or receiver 412. In one embodiment, theincident light may be guided by a fiber optic through the light guide405, and the reflected light may be captured by a series of fibersforming a bundle adjacent to or surrounding the incident light fiber.

In another embodiment, a “clamp” design 500 may be used as a cap overone or more teeth, as illustrated in FIG. 5A. The clamp design may bedifferent for different types of teeth, or it may be flexible enough tofit over different types of teeth. For example, different types of teethinclude the molars (toward the back of the mouth), the premolars, thecanine, and the incisors (toward the front of the mouth). One embodimentof the clamp-type design is illustrated in FIG. 5A for a molar tooth508. The C-clamp 501 may be made of a plastic or rubber material, and itmay comprise a light source input 502 and a detector output 503 on thefront or back of the tooth, for example.

The light source input 502 may comprise a light source directly, or itmay have light guided to it from an external light source. Also, thelight source input 502 may comprise a lens system to collimate or focusthe light across the tooth. The detector output 503 may comprise adetector directly, or it may have a light guide to transport the signalto an external detector element. The light source input 502 may becoupled electrically or optically through 504 to a light input 506. Forexample, if the light source is external in 506, then the couplingelement 504 may be a light guide, such as a fiber optic. Alternately, ifthe light source is contained in 502, then the coupling element 504 maybe electrical wires connecting to a power supply in 506. Similarly, thedetector output 503 may be coupled to a detector output unit 507 with acoupling element 505, which may be one or more electrical wires or alight guide, such as a fiber optic. This is just one example of a clampover one or more teeth, but other embodiments may also be used and areintended to be covered by this disclosure. For example, if reflectancefrom the teeth is to be used in the measurement, then the light input502 and detected light input 503 may be on the same side of the tooth.

In yet another embodiment, one or more light source ports and sensorports may be used in a mouth-guard type design. For example, oneembodiment of a dental mouth guard 550 is illustrated in FIG. 5B. Thestructure of the mouth guard 551 may be similar to mouth guards used insports (e.g., when playing football or boxing) or in dental trays usedfor applying fluoride treatment, and the mouth guard may be made fromplastic, rubber, or any other suitable materials. As an example, themouth guard may have one or more light source input ports 552, 553 andone or more detector output ports 554, 555. Although six input andoutput ports are illustrated, any number of ports may be used.

Similar to the clamp design described above, the light source inputs552, 553 may comprise one or more light sources directly, or they mayhave light guided to them from an external light source. Also, the lightsource inputs 552, 553 may comprise lens systems to collimate or focusthe light across the teeth. The detector outputs 554, 555 may compriseone or more detectors directly, or they may have one or more lightguides to transport the signals to an external detector element. Thelight source inputs 552, 553 may be coupled electrically or opticallythrough 556 to a light input 557. For example, if the light source isexternal in 557, then the one or more coupling elements 556 may be oneor more light guides, such as a fiber optic. Alternately, if the lightsources are contained in 552, 553, then the coupling element 556 may beone or more electrical wires connecting to a power supply in 557.Similarly, the detector outputs 554, 555 may be coupled to a detectoroutput unit 559 with one or more coupling elements 558, which may be oneor more electrical wires or one or more light guides, such as a fiberoptic. This is just one example of a mouth guard design covering aplurality of teeth, but other embodiments may also be used and areintended to be covered by this disclosure. For instance, the position ofthe light source inputs and detector output ports could be exchanged, orsome mixture of locations of light source inputs and detector outputports could be used. Also, if reflectance from the teeth is to bemeasured, then the light sources and detectors may be on the same sideof the tooth. Moreover, it may be advantageous to pulse the light sourcewith a particular pulse width and pulse repetition rate, and then thedetection system can measure the pulsed light returned from ortransmitted through the tooth. Using a lock-in type technique (e.g.,detecting at the same frequency as the pulsed light source and alsopossibly phase locked to the same signal), the detection system may beable to reject background or spurious signals and increase thesignal-to-noise ratio of the measurement.

Other elements may be added to the human interface designs of FIGS. 4-6and are also intended to be covered by this disclosure. For instance, inone embodiment it may be desirable to have replaceable inserts that maybe disposable. Particularly in a dentist's or doctor's office orhospital setting, the same instrument may be used with a plurality ofpatients. Rather than disinfecting the human interface after each use,it may be preferable to have disposable inserts that can be thrown awayafter each use. In one embodiment, a thin plastic coating material mayenclose the clamp design of FIG. 5A or mouth guard design of FIG. 5B.The coating material may be inserted before each use, and then after themeasurement is exercised the coating material may be peeled off andreplaced. The coating or covering material may be selected based onsuitable optical properties that do not affect the measurement, or knownoptical properties that can be calibrated or compensated for duringmeasurement. Such a design may save the dentist or physician or userconsiderable time, while at the same time provide the business venturewith a recurring cost revenue source.

Thus, beyond the problem of other blood constituents or analytes havingoverlapping spectral features, it may be difficult to observe glucosespectral signatures through the skin and its constituents of water,adipose, collagen and elastin. One approach to overcoming thisdifficulty may be to try to measure the blood constituents in veins thatare located at relatively shallow distances below the skin. Veins may bemore beneficial for the measurement than arteries, since arteries tendto be located at deeper levels below the skin. Also, in one embodimentit may be advantageous to use a differential measurement to subtract outsome of the interfering absorption lines from the skin. For example, aninstrument head may be designed to place one probe above a region ofskin over a blood vein, while a second probe may be placed at a regionof the skin without a noticeable blood vein below it. Then, bydifferencing the signals from the two probes, at least part of the skininterference may be cancelled out.

Two representative embodiments for performing such a differentialmeasurement are illustrated in FIG. 6A and FIG. 6B. In one embodimentshown in FIG. 6A, the dorsal of the hand 600 may be used for measuringblood constituents or analytes. The dorsal of the hand 600 may haveregions that have distinct veins 601 as well as regions where the veinsare not as shallow or pronounced 602. By stretching the hand and leaningit backwards, the veins 601 may be accentuated in some cases. Anear-infrared diffuse reflectance measurement may be performed byplacing one probe 603 above the vein-rich region 601. To turn this intoa differential measurement, a second probe 604 may be placed above aregion without distinct veins 602. Then, the outputs from the two probesmay be subtracted 605 to at least partially cancel out the features fromthe skin. The subtraction may be done preferably in the electricaldomain, although it can also be performed in the optical domain ordigitally/mathematically using sampled data based on the electricaland/or optical signals. Although one example of using the dorsal of thehand 600 is shown, many other parts of the hand can be used within thescope of this disclosure. For example, alternate methods may usetransmission through the webbing between the thumb and the fingers 606,or transmission or diffuse reflection through the tips of the fingers607.

In another embodiment, the dorsal of the foot 650 may be used instead ofthe hand. One advantage of such a configuration may be that forself-testing by a user, the foot may be easier to position theinstrument using both hands. One probe 653 may be placed over regionswhere there are more distinct veins 651, and a near-infrared diffusereflectance measurement may be made. For a differential measurement, asecond probe 654 may be placed over a region with less prominent veins652, and then the two probe signals may be subtracted, eitherelectronically or optically, or may be digitized/sampled and processedmathematically depending on the particular application andimplementation. As with the hand, the differential measurements may beintended to compensate for or subtract out (at least in part) theinterference from the skin. Since two regions are used in closeproximity on the same body part, this may also aid in removing somevariability in the skin from environmental effects such as temperature,humidity, or pressure. In addition, it may be advantageous to firsttreat the skin before the measurement, by perhaps wiping with a cloth ortreated cotton ball, applying some sort of cream, or placing an ice cubeor chilled bag over the region of interest.

Although two embodiments have been described, many other locations onthe body may be used using a single or differential probe within thescope of this disclosure. In yet another embodiment, the wrist may beadvantageously used, particularly where a pulse rate is typicallymonitored. Since the pulse may be easily felt on the wrist, there isunderlying the region a distinct blood flow. Other embodiments may useother parts of the body, such as the ear lobes, the tongue, the innerlip, the nails, the eye, or the teeth. Some of these embodiments will befurther described below. The ear lobes or the tip of the tongue may beadvantageous because they are thinner skin regions, thus permittingtransmission rather than diffuse reflection. However, the interferencefrom the skin is still a problem in these embodiments. Other regionssuch as the inner lip or the bottom of the tongue may be contemplatedbecause distinct veins are observable, but still the interference fromthe skin may be problematic in these embodiments. The eye may seem as aviable alternative because it is more transparent than skin. However,there are still issues with scattering in the eye. For example, theanterior chamber of the eye (the space between the cornea and the iris)comprises a fluid known as aqueous humor. However, the glucose level inthe eye chamber may have a significant temporal lag on changes in theglucose level compared to the blood glucose level.

One of the issues in measuring a particular blood constituent is theinterfering and overlapping signal from other blood constituents. Theselection of the constituent of interest may be improved using a numberof techniques. For example, a higher light level or intensity mayimprove the signal-to-noise ratio for the measurement. Second,mathematical modeling and signal processing methodologies may help toreduce the interference, such as multivariate techniques, multiplelinear regression, and factor-based algorithms, for example. Forinstance, a number of mathematical approaches include multiple linearregression, partial least squares, and principal component regression(PCR). Various mathematical derivatives, including the first and secondderivatives, may help to accentuate differences between spectra. Inaddition, by using a wider wavelength range and using more samplingwavelengths may improve the ability to discriminate one signal fromanother. These are just examples of some of the methods of improving theability to discriminate between different constituents, but othertechniques may also be used and are intended to be covered by thisdisclosure.

Light Sources for Near Infrared

There are a number of light sources that may be used in the nearinfrared. To be more specific, the discussion below will consider lightsources operating in the short wave infrared (SWIR), which may cover thewavelength range of approximately 1400 nm to 2500 nm. Other wavelengthranges may also be used for the applications described in thisdisclosure, so the discussion below is merely provided as exemplarytypes of light sources. The SWIR wavelength range may be valuable for anumber of reasons. First, the SWIR corresponds to a transmission windowthrough water and the atmosphere. Second, the so-called “eye-safe”wavelengths are wavelengths longer than approximately 1400 nm. Third,the SWIR covers the wavelength range for nonlinear combinations ofstretching and bending modes as well as the first overtone of C—Hstretching modes. Thus, for example, glucose and ketones among othersubstances may have unique signatures in the SWIR. Moreover, many solidshave distinct spectral signatures in the SWIR, so particular solids maybe identified using stand-off detection or remote sensing. For instance,many explosives have unique signatures in the SWIR.

Different light sources may be selected for the SWIR based on the needsof the application. Some of the features for selecting a particularlight source include power or intensity, wavelength range or bandwidth,spatial or temporal coherence, spatial beam quality for focusing ortransmission over long distance, and pulse width or pulse repetitionrate. Depending on the application, lamps, light emitting diodes (LEDs),laser diodes (LD's), tunable LD's, super-luminescent laser diodes(SLDs), fiber lasers or super-continuum sources (SC) may beadvantageously used. Also, different fibers may be used for transportingthe light, such as fused silica fibers, plastic fibers, mid-infraredfibers (e.g., tellurite, chalcogenides, fluorides, ZBLAN, etc), or ahybrid of these fibers.

Lamps may be used if low power or intensity of light is required in theSWIR, and if an incoherent beam is suitable. In one embodiment, in theSWIR an incandescent lamp that can be used is based on tungsten andhalogen, which have an emission wavelength between approximately 500 nmto 2500 nm. For low intensity applications, it may also be possible touse thermal sources, where the SWIR radiation is based on the black bodyradiation from the hot object. Although the thermal and lamp basedsources are broadband and have low intensity fluctuations, it may bedifficult to achieve a high signal-to-noise ratio due to the low powerlevels. Also, the lamp based sources tend to be energy inefficient.

In another embodiment, LED's can be used that have a higher power levelin the SWIR wavelength range. LED's also produce an incoherent beam, butthe power level can be higher than a lamp and with higher energyefficiency. Also, the LED output may more easily be modulated, and theLED provides the option of continuous wave or pulsed mode of operation.LED's are solid state components that emit a wavelength band that is ofmoderate width, typically between about 20 nm to 40 nm. There are alsoso-called super-luminescent LEDs that may even emit over a much widerwavelength range. In another embodiment, a wide band light source may beconstructed by combining different LEDs that emit in differentwavelength bands, some of which could preferably overlap in spectrum.One advantage of LEDs as well as other solid state components is thecompact size that they may be packaged into.

In yet another embodiment, various types of laser diodes may be used inthe SWIR wavelength range. Just as LEDs may be higher in power butnarrower in wavelength emission than lamps and thermal sources, the LDsmay be yet higher in power but yet narrower in wavelength emission thanLEDs. Different kinds of LDs may be used, including Fabry-Perot LDs,distributed feedback (DFB) LDs, distributed Bragg reflector (DBR) LDs.Since the LDs have relatively narrow wavelength range (typically under10 nm), in one embodiment a plurality of LDs may be used that are atdifferent wavelengths in the SWIR. The various LDs may be spatiallymultiplexed, polarization multiplexed, wavelength multiplexed, or acombination of these multiplexing methods. Also, the LDs may be fiberpig-tailed or have one or more lenses on the output to collimate orfocus the light. Another advantage of LDs is that they may be packagedcompactly and may have a spatially coherent beam output. Moreover,tunable LDs that can tune over a range of wavelengths are alsoavailable. The tuning may be done by varying the temperature, orelectrical current may be used in particular structures such asdistributed Bragg reflector (DBR) LDs, for example. In anotherembodiment, external cavity LDs may be used that have a tuning element,such as a fiber grating or a bulk grating, in the external cavity.

In another embodiment, super-luminescent laser diodes may provide higherpower as well as broad bandwidth. An SLD is typically an edge emittingsemiconductor light source based on super-luminescence (e.g., this couldbe amplified spontaneous emission). SLDs combine the higher power andbrightness of LDs with the low coherence of conventional LEDs, and theemission band for SLD's may be 5 to 100 nm wide, preferably in the 60 to100 nm range. Although currently SLDs are commercially available in thewavelength range of approximately 400 nm to 1700 nm, SLDs could and mayin the future be made to cover a broader region of the SWIR.

In yet another embodiment, high power LDs for either direct excitationor to pump fiber lasers and SC light sources may be constructed usingone or more laser diode bar stacks. FIG. 7 shows an example of a blockdiagram 700 or building blocks for constructing the high power LDs. Inthis embodiment, one or more diode bar stacks 701 may be used, where thediode bar stack may be an array of several single emitter LDs. Since thefast axis (e.g., vertical direction) may be nearly diffraction limitedwhile the slow-axis (e.g., horizontal axis) may be far from diffractionlimited, different collimators 702 may be used for the two axes.

Then, the brightness may be increased by spatially combining the beamsfrom multiple stacks 703. The combiner may include spatial interleaving,it may include wavelength multiplexing, or it may involve a combinationof the two. Different spatial interleaving schemes may be used, such asusing an array of prisms or mirrors with spacers to bend one array ofbeams into the beam path of the other. In another embodiment, segmentedmirrors with alternate high-reflection and anti-reflection coatings maybe used. Moreover, the brightness may be increased by polarization beamcombining 704 the two orthogonal polarizations, such as by using apolarization beam splitter. In a particular embodiment, the output maythen be focused or coupled into a large diameter core fiber. As anexample, typical dimensions for the large diameter core fiber range fromdiameters of approximately 100 microns to 400 microns or more.Alternatively or in addition, a custom beam shaping module 705 may beused, depending on the particular application. For example, the outputof the high power LD may be used directly 706, or it may be fibercoupled 707 to combine, integrate, or transport the high power LDenergy. These high power LDs may grow in importance because the LDpowers can rapidly scale up. For example, instead of the power beinglimited by the power available from a single emitter, the power mayincrease in multiples depending on the number of diodes multiplexed andthe size of the large diameter fiber. Although FIG. 7 is shown as oneembodiment, some or all of the elements may be used in a high power LD,or additional elements may also be used.

As described in greater detail in commonly owned US Pat. App. Pub.2014/0188094, in some instances, it may be desirable to create multiplelocations of focused light. For example, the speed of the treatment forvaricose veins may be increased by causing thermal coagulation orocclusion at multiple locations. Multiple collimated or focused lightbeams may be created in one assembly. In such embodiments, optionally asurface cooling apparatus may be used, where a cooling fluid may beflowed either touching or in close proximity to the skin. Also, in thisparticular embodiment a cylindrical assembly may optionally be used,where the cylindrical length may be several millimeters in length anddefined by a clamp or mount placed on or near the leg. In oneembodiment, a window and/or lenslet array is also shown on thecylindrical surface for permitting the light to be incident on the skinand varicose vein at multiple spots. The lenslet array may comprisecircular, spherical or cylindrical lenses, depending on the type ofspots desired. As before, one advantage of placing the lenslet array inclose proximity to the skin and varicose vein may be that a high NA lensmay be used. Also, the input from the lens and/or mirror assembly to thelenslet array may be single large beam, or a plurality of smaller beams.In one embodiment, a plurality of spots may be created by the lensletarray to cause a plurality of locations of thermal coagulation in thevaricose vein. Any number of spots may be used and are intended to becovered by this disclosure.

In a non-limiting example, a plurality of spots may be used, or whatmight be called a fractionated beam. The fractionated laser beam may beadded to the laser delivery assembly or delivery head in a number ofways. In one embodiment, a screen-like spatial filter may be placed inthe pathway of the beam to be delivered to the biological tissue. Thescreen-like spatial filter can have opaque regions to block the lightand holes or transparent regions, through which the laser beam may passto the tissue sample. The ratio of opaque to transparent regions may bevaried, depending on the application of the laser. In anotherembodiment, a lenslet array can be used at or near the output interfacewhere the light emerges. In yet another embodiment, at least a part ofthe delivery fiber from the infrared laser system to the delivery headmay be a bundle of fibers, which may comprise a plurality of fiber coressurrounded by cladding regions. The fiber cores can then correspond tothe exposed regions, and the cladding areas can approximate the opaqueareas not to be exposed to the laser light. As an example, a bundle offibers may be excited by at least a part of the laser system output, andthen the fiber bundle can be fused together and perhaps pulled down to adesired diameter to expose to the tissue sample near the delivery head.In yet another embodiment, a photonic crystal fiber may be used tocreate the fractionated laser beam. In one non-limiting example, thephotonic crystal fiber can be coupled to at least a part of the lasersystem output at one end, and the other end can be coupled to thedelivery head. In a further example, the fractionated laser beam may begenerated by a heavily multi-mode fiber, where the speckle pattern atthe output may create the high intensity and low intensity spatialpattern at the output. Although several exemplary techniques areprovided for creating a fractionated laser beam, other techniques thatcan be compatible with optical fibers are also intended to be includedby this disclosure.

Although the output from a fiber laser may be from a single ormulti-mode fiber, different spatial spot sizes or spatial profiles maybe beneficial for different applications. For example, in some instancesit may be desirable to have a series of spots or a fractionated beamwith a grid of spots. In one embodiment, a bundle of fibers or a lightpipe with a plurality of guiding cores may be used. In anotherembodiment, one or more fiber cores may be followed by a lenslet arrayto create a plurality of collimated or focused beams. In yet anotherembodiment, a delivery light pipe may be followed by a grid-likestructure to divide up the beam into a plurality of spots. These arespecific examples of beam shaping, and other apparatuses and methods mayalso be used and are consistent with this disclosure.

SWIR Super-continuum Lasers

Each of the light sources described above have particular strengths, butthey also may have limitations. For example, there is typically atrade-off between wavelength range and power output. Also, sources suchas lamps, thermal sources, and LEDs produce incoherent beams that may bedifficult to focus to a small area and may have difficulty propagatingfor long distances. An alternative source that may overcome some ofthese limitations is an SC light source. Some of the advantages of theSC source may include high power and intensity, wide bandwidth,spatially coherent beam that can propagate nearly transform limited overlong distances, and easy compatibility with fiber delivery.

Supercontinuum lasers may combine the broadband attributes of lamps withthe spatial coherence and high brightness of lasers. By exploiting amodulational instability initiated supercontinuum (SC) mechanism, anall-fiber-integrated SC laser with no moving parts may be built usingcommercial-off-the-shelf (COTS) components. Moreover, the fiber laserarchitecture may be a platform where SC in the visible,near-infrared/SWIR, or mid-IR can be generated by appropriate selectionof the amplifier technology and the SC generation fiber. But untilrecently, SC lasers were used primarily in laboratory settings sincetypically large, table-top, mode-locked lasers were used to pumpnonlinear media such as optical fibers to generate SC light. However,those large pump lasers may now be replaced with diode lasers and fiberamplifiers that gained maturity in the telecommunications industry.

In one embodiment, an all-fiber-integrated, high-powered SC light source800 may be elegant for its simplicity (FIG. 8). The light may be firstgenerated from a seed laser diode 801. For example, the seed LD 801 maybe a distributed feedback (DFB) laser diode with a wavelength near 1542or 1550 nm, with approximately 0.5-2.0 ns pulsed output, and with apulse repetition rate between about one kilohertz to about 100 MHz ormore. The output from the seed laser diode may then be amplified in amultiple-stage fiber amplifier 802 comprising one or more gain fibersegments. In one embodiment, the first stage pre-amplifier 803 may bedesigned for optimal noise performance. For example, the pre-amplifier803 may be a standard erbium-doped fiber amplifier or anerbium/ytterbium doped cladding pumped fiber amplifier. Betweenamplifier stages 803 and 806, it may be advantageous to use band-passfilters 804 to block amplified spontaneous emission and isolators 805 toprevent spurious reflections. Then, the power amplifier stage 806 mayuse a cladding-pumped fiber amplifier that may be optimized to minimizenonlinear distortion. The power amplifier fiber 806 may also be anerbium-doped fiber amplifier, if only low or moderate power levels areto be generated.

The SC generation 807 may occur in the relatively short lengths of fiberthat follow the pump laser. The SC fiber length may range from around afew millimeters to 100 m or more. In one embodiment, the SC generationmay occur in a first fiber 808 where the modulational-instabilityinitiated pulse break-up occurs primarily, followed by a second fiber809 where the SC generation and spectral broadening occurs primarily.

In one embodiment, one or two meters of standard single-mode fiber (SMF)after the power amplifier stage may be followed by several meters of SCgeneration fiber. For this example, in the SMF the peak power may beseveral kilowatts and the pump light may fall in the anomalousgroup-velocity dispersion regime—often called the soliton regime. Forhigh peak powers in the anomalous dispersion regime, the nanosecondpulses may be unstable due to a phenomenon known as modulationalinstability, which is basically parametric amplification in which thefiber nonlinearity helps to phase match the pulses. As a consequence,the nanosecond pump pulses may be broken into many shorter pulses as themodulational instability tries to form soliton pulses from thequasi-continuous-wave background. Although the laser diode andamplification process starts with approximately nanosecond-long pulses,modulational instability in the short length of SMF fiber may formapproximately 0.5 ps to several-picosecond-long pulses with highintensity. Thus, the few meters of SMF fiber may result in an outputsimilar to that produced by mode-locked lasers, except in a much simplerand cost-effective manner.

The short pulses created through modulational instability may then becoupled into a nonlinear fiber for SC generation. The nonlinearmechanisms leading to broadband SC may include four-wave mixing orself-phase modulation along with the optical Raman effect. Since theRaman effect is self-phase-matched and shifts light to longerwavelengths by emission of optical photons, the SC may spread to longerwavelengths very efficiently. The short-wavelength edge may arise fromfour-wave mixing, and often times the short wavelength edge may belimited by increasing group-velocity dispersion in the fiber. In manyinstances, if the particular fiber used has sufficient peak power and SCfiber length, the SC generation process may fill the long-wavelengthedge up to the transmission window.

Mature fiber amplifiers for the power amplifier stage 806 includeytterbium-doped fibers (near 1060 nm), erbium-doped fibers (near 1550nm), erbium/ytterbium-doped fibers (near 1550 nm), or thulium-dopedfibers (near 2000 nm). In various embodiments, candidates for SC fiber809 include fused silica fibers (for generating SC between 0.8-2.7 μm),mid-IR fibers such as fluorides, chalcogenides, or tellurites (forgenerating SC out to 4.5 μm or longer), photonic crystal fibers (forgenerating SC between 0.4 and 1.7 μm), or combinations of these fibers.Therefore, by selecting the appropriate fiber-amplifier doping for 806and nonlinear fiber 809, SC may be generated in the visible,near-IR/SWIR, or mid-IR wavelength region.

The configuration 800 of FIG. 8 is just one particular example, andother configurations can be used and are intended to be covered by thisdisclosure. For example, further gain stages may be used, and differenttypes of lossy elements or fiber taps may be used between the amplifierstages. In another embodiment, the SC generation may occur partially inthe amplifier fiber and in the pig-tails from the pump combiner or otherelements. In yet another embodiment, polarization maintaining fibers maybe used, and a polarizer may also be used to enhance the polarizationcontrast between amplifier stages. Also, not discussed in detail aremany accessories that may accompany this set-up, such as driverelectronics, pump laser diodes, safety shut-offs, and thermal managementand packaging.

In one embodiment, one example of the SC laser that operates in the SWIRis illustrated in FIG. 9. This SWIR SC source 900 produces an output ofup to approximately 5 W over a spectral range of about 1.5 to 2.4microns, and this particular laser is made out of polarizationmaintaining components. The seed laser 901 is a distributed feedback(DFB) laser operating near 1542 nm producing approximately 0.5 nsecpulses at an about 8 MHz repetition rate. The pre-amplifier 902 isforward pumped and uses about 2 m length of erbium/ytterbium claddingpumped fiber 903 (often also called dual-core fiber) with an inner corediameter of 12 microns and outer core diameter of 130 microns. Thepre-amplifier gain fiber 903 is pumped using a 10 W laser diode near 940nm 905 that is coupled in using a fiber combiner 904.

In this particular 5 W unit, the mid-stage between amplifier stages 902and 906 comprises an isolator 907, a band-pass filter 908, a polarizer909 and a fiber tap 910. The power amplifier 906 uses an approximately 4m length of the 12/130 micron erbium/ytterbium doped fiber 911 that iscounter-propagating pumped using one or more 30 W laser diodes near 940nm 912 coupled in through a combiner 913. An approximately 1-2 meterlength of the combiner pig-tail helps to initiate the SC process, andthen a length of PM-1550 fiber 915 (polarization maintaining,single-mode, fused silica fiber optimized for 1550 nm) is spliced 914 tothe combiner output.

If an output fiber of about 10 m in length is used, then the resultingoutput spectrum 1000 is shown in FIG. 10. The details of the outputspectrum 1000 depend on the peak power into the fiber, the fiber length,and properties of the fiber such as length and core size, as well as thezero dispersion wavelength and the dispersion properties. For example,if a shorter length of fiber is used, then the spectrum actually reachesto longer wavelengths (e.g., a 2 m length of SC fiber broadens thespectrum to about 2500 nm). Also, if extra-dry fibers are used with lessO—H content, then the wavelength edge may also reach to a longerwavelength. To generate more spectra toward the shorter wavelengths, thepump wavelength (in this case ˜1542 nm) should be close to the zerodispersion wavelength in the fiber. For example, by using a dispersionshifted fiber or so-called non-zero dispersion shifted fiber, the shortwavelength edge may shift to shorter wavelengths.

In one particular embodiment, the SWIR-SC light source of FIG. 9 withoutput spectrum in FIG. 10 was used in preliminary experiments forexamining the reflectance from different dental samples. A schematic ofthe experimental set-up 1100 for measuring the diffuse reflectancespectroscopy is illustrated in FIG. 11A. The SC source 1101 in thisembodiment was based on the design of FIG. 9 and delivered approximately1.6 W of light over the wavelength range from about 1500-2400 nm. Theoutput beam 1102 was collimated, and then passed through a chopper 1103(for lock-in detection at the receiver after the spectrometer 1106) andan aperture 1104 for localizing the beam on the tooth location.Different teeth 1105 with different lesions and caries were placed infront of the aperture 1104, and the scattered light was passed through aspectrometer 1106 and collected on a detector, whose signal was sent toa receiver. The tooth samples 1105 were mounted in clay or putty forstanding upright. Different types of teeth could be used, includingmolars, premolars, canine and incisor teeth.

FIG. 11B shows exemplary reflectance spectra 1150 from a sound enamelregion 1151 (e.g., without dental caries), an enamel lesion region 1152,and a dentine lesion region 1153 of various teeth. The spectra arenormalized to have equal value near 2050 nm. In this particularembodiment, the slope from the sound enamel 1151 is steepest betweenabout 1500 and 1950 nm, with a lesser slope in the presence of an enamellesion 1152. When there is a sample with dentine lesion 1153, morefeatures appear in the spectrum from the presence of water absorptionlines from water that collects in the dentine. For this experiment, thespectra 1151, 1152, and 1153 are flatter in the wavelength regionbetween about 1950 nm and 2350 nm. These are preliminary results, butthey show the benefit of using broadband sources such as the SWIR-SCsource for diagnosing dental caries. Although the explanation behind thedifferent spectra 1150 of FIG. 11B may not be understood as yet, it isclear that the spectra 1151, 1152 and 1153 are distinguishable.Therefore, the broadband reflectance may be used for detection of dentalcaries and analyzing the region of the caries. Although diffusereflectance has been used in this experiment, other signals, such astransmission, reflectance or a combination, may also be used and arecovered by this disclosure.

Although one particular example of a 5 W SWIR-SC has been described,different components, different fibers, and different configurations mayalso be used consistent with this disclosure. For instance, anotherembodiment of the similar configuration 900 in FIG. 9 may be used togenerate high powered SC between approximately 1060 and 1800 nm. Forthis embodiment, the seed laser 901 may be a distributed feedback laserdiode of about 1064 nm, the pre-amplifier gain fiber 903 may be aytterbium-doped fiber amplifier with 10/125 microns dimensions, and thepump laser 905 may be a 10 W laser diode near 915 nm. A mode fieldadapter may be including in the mid-stage, in addition to the isolator907, band pass filter 908, polarizer 909 and tap 910. The gain fiber 911in the power amplifier may be an about 20 m length of ytterbium-dopedfiber with 25/400 microns dimension. The pump 912 for the poweramplifier may be up to six pump diodes providing 30 W each near 915 nm.For this much pump power, the output power in the SC may be as high as50 W or more.

In an alternate embodiment, it may be desirous to generate high powerSWIR SC over 1.4-1.8 microns and separately 2-2.5 microns (the windowbetween 1.8 and 2 microns may be less important due to the strong waterand atmospheric absorption). For example, the SC source of FIG. 12A canlead to bandwidths ranging from about 1400 nm to 1800 nm or broader,while the SC source of FIG. 12B can lead to bandwidths ranging fromabout 1900 nm to 2500 nm or broader. Since these wavelength ranges areshorter than about 2500 nm, the SC fiber can be based on fused silicafiber. Exemplary SC fibers include standard single-mode fiber (SMF),high-nonlinearity fiber, high-NA fiber, dispersion shifted fiber,dispersion compensating fiber, and photonic crystal fibers.Non-fused-silica fibers can also be used for SC generation, includingchalcogenides, fluorides, ZBLAN, tellurites, and germanium oxide fibers.

In one embodiment, FIG. 12A illustrates a block diagram for an SC source1200 capable of generating light between approximately 1400 nm and 1800nm or broader. As an example, a pump fiber laser similar to FIG. 9 canbe used as the input to a SC fiber 1209. The seed laser diode 1201 cancomprise a DFB laser that generates, for example, several milliwatts ofpower around 1542 nm or 1553 nm. The fiber pre-amplifier 1202 cancomprise an erbium-doped fiber amplifier or an erbium/ytterbium dopeddouble clad fiber. In this example, a mid-stage amplifier 1203 can beused, which can comprise an erbium/ytterbium doped double-clad fiber. Abandpass filter 1205 and isolator 1206 may be used between thepre-amplifier 1202 and mid-stage amplifier 1203. The power amplifierstage 1204 can comprise a larger core size erbium/ytterbium dopeddouble-clad fiber, and another bandpass filter 1207 and isolator 1208can be used before the power amplifier 1204. The output of the poweramplifier can be coupled to the SC fiber 1209 to generate the SC output1210. This is just one exemplary configuration for an SC source, andother configurations or elements may be used consistent with thisdisclosure.

In yet another embodiment, FIG. 12B illustrates a block diagram for anSC source 1250 capable of generating light between approximately 1900and 2500 nm or broader. As an example, the seed laser diode 1251 cancomprise a DFB or DBR laser that generates, for example, severalmilliwatts of power around 1542 nm or 1553 nm. The fiber pre-amplifier1252 can comprise an erbium-doped fiber amplifier or an erbium/ytterbiumdoped double-clad fiber. In this example, a mid-stage amplifier 1253 canbe used, which can comprise an erbium/ytterbium doped double-clad fiber.A bandpass filter 1255 and isolator 1256 may be used between thepre-amplifier 1252 and mid-stage amplifier 1253. The power amplifierstage 1254 can comprise a thulium doped double-clad fiber, and anotherisolator 1257 can be used before the power amplifier 1254. Note that theoutput of the mid-stage amplifier 1253 can be approximately near 1542nm, while the thulium-doped fiber amplifier 1254 can amplify wavelengthslonger than approximately 1900 nm and out to about 2100 nm. Therefore,for this configuration wavelength shifting may be required between 1253and 1254. In one embodiment, the wavelength shifting can be accomplishedusing a length of standard single-mode fiber 1258, which can have alength between approximately 5 and 50 meters, for example. The output ofthe power amplifier 1254 can be coupled to the SC fiber 1259 to generatethe SC output 1260. This is just one exemplary configuration for an SCsource, and other configurations or elements can be used consistent withthis disclosure. For example, the various amplifier stages can comprisedifferent amplifier types, such as erbium doped fibers, ytterbium dopedfibers, erbium/ytterbium co-doped fibers and thulium doped fibers.

FIG. 12C illustrates a reflection-spectroscopy based stand-off detectionsystem having an SC laser source. The set-up 1270 for thereflection-spectroscopy-based stand-off detection system includes an SCsource 1271. First, the diverging SC output is collimated to a 1 cmdiameter beam using a 25 mm focal length, 90 degrees off-axis, goldcoated, parabolic mirror 1272. To reduce the effects of chromaticaberration, refractive optics are avoided in the setup. All focusing andcollimation is done using metallic mirrors that have almost constantreflectivity and focal length over the entire SC output spectrum. Thesample 1274 is kept at a distance from the collimating mirror 1272,which provides a total round trip path length of twice the distancebefore reaching the collection optics 1275. A 12 cm diameter silvercoated concave mirror 1275 with a 75 cm focal length is kept 20 cm tothe side of the collimation mirror 1272. The mirror 1275 is used tocollect a fraction of the diffusely reflected light from the sample, andfocus it into the input slit of a monochromator 1276. Thus, the beam isincident normally on the sample 1274, but detected at a reflection angleof tan⁻¹(0.2/5) or about 2.3 degrees. Appropriate long wavelength passfilters mounted in a motorized rotating filter wheel are placed in thebeam path before the input slit 1276 to avoid contribution from higherwavelength orders from the grating (300 grooves/mm, 2 μm blaze). Theoutput slit width is set to 2 mm corresponding to a spectral resolutionof 10.8 nm, and the light is detected by a 2 mm×2 mm liquid nitrogencooled (77K) indium antimonide (InSb) detector 1277. The detected outputis amplified using a trans-impedance pre-amplifier 1277 with a gain ofabout 105 V/A and connected to a lock-in amplifier 1278 setup for highsensitivity detection. The chopper frequency is 400 Hz, and the lock-intime constant is set to 100 ms corresponding to a noise bandwidth ofabout 1 Hz. These are exemplary elements and parameter values, but otheror different optical elements may be used consistent with thisdisclosure.

While the above detection systems could be categorized as single pathdetection systems, it may be advantageous in some cases to usemulti-path detection systems. In one embodiment, a detection system froma Fourier transform infrared spectrometer, FTIR, may be used. Thereceived light may be incident on a particular configuration of mirrors,called a Michelson interferometer, that allows some wavelengths to passthrough but blocks others due to wave interference. The beam may bemodified for each new data point by moving one of the mirrors, whichchanges the set of wavelengths that pass through. This collected data iscalled an interferogram. The interferogram is then processed, typicallyon a computing system, using an algorithm called the Fourier transform.One advantageous feature of FTIR is that it may simultaneously collectspectral data in a wide spectral range.

Another advantage of using the near-infrared or SWIR is that most drugpackaging materials are at least partially transparent in thiswavelength range, so that drug compositions may be detected andidentified through the packaging non-destructively. As an example, SWIRlight could be used to see through plastics, since the signature forplastics can be subtracted off and there are large wavelength windowswhere the plastics are transparent. Because of the hydro-carbon bonds,there are absorption features near 1.7 microns and 2.2-2.5 microns. Ingeneral, the absorption bands in the near infrared are due to overtonesand combination bands for various functional group vibrations, includingsignals from C—H, O—H, C═O, N—H, —COOH, and aromatic C—H groups. It maybe difficult to assign an absorption band to a specific functional groupdue to overlapping of several combinations and overtones. However, withadvancements in computational power and chemometrics or multivariateanalysis methods, complex systems may be better analyzed. In oneembodiment, using software analysis tools the absorption spectrum may beconverted to its second derivative equivalent. The spectral differencesmay permit a fast, accurate, non-destructive and reliable identificationof materials. Although particular derivatives are discussed, othermathematical manipulations may be used in the analysis, and these othertechniques are also intended to be covered by this disclosure.

Described herein are just some examples of the beneficial use ofnear-infrared or SWIR lasers for spectroscopy, active remote sensing orhyper-spectral imaging. However, many other spectroscopy andidentification procedures can use the near-infrared or SWIR lightconsistent with this disclosure and are intended to be covered by thedisclosure. As one example, the fiber-based super-continuum lasers mayhave a pulsed output with pulse durations of approximately 0.5-2 nsecand pulse repetition rates of several Megahertz. Therefore, thenear-infrared or SWIR spectroscopy, active remote sensing orhyper-spectral imaging applications may also be combined with LIDAR-typeapplications. Namely, the distance or time axis can be added to theinformation based on time-of-flight measurements. For this type ofinformation to be used, the detection system would also have to betime-gated to be able to measure the time difference between the pulsessent and the pulses received. By calculating the round-trip time for thesignal, the distance of the object may be judged. In another embodiment,GPS (global positioning system) information may be added, so thenear-infrared or SWIR spectroscopy, active remote sensing orhyper-spectral imagery would also have a location tag on the data.Moreover, the near-infrared or SWIR spectroscopy, active remote sensingor hyper-spectral imaging information could also be combined withtwo-dimensional or three-dimensional images to provide a physicalpicture as well as a chemical composition identification of thematerials. These are just some modifications of the near-infrared orSWIR spectroscopy, active remote sensing or hyper-spectral imagingsystem described in this disclosure, but other techniques may also beadded or combinations of these techniques may be added, and these arealso intended to be covered by this disclosure.

In yet another example of multi-beam detection systems, a dual-beamset-up 1280 such as in FIG. 12D may be used to subtract out (or at leastminimize the adverse effects of) light source fluctuations. In oneembodiment, the output from an SC source 1281 may be collimated using aCaF2 lens 1282 and then focused into the entrance slit of themonochromator 1283. At the exit slit, light at the selected wavelengthis collimated again and may be passed through a polarizer 1284 beforebeing incident on a calcium fluoride beam splitter 1285. After passingthrough the beam splitter 1285, the light is split into a sample 1286and reference 1287 arm to enable ratiometric detection that may cancelout effects of intensity fluctuations in the SC source 1281. The lightin the sample arm 1286 passes through the sample of interest and is thenfocused onto a HgCdTe detector 1288 connected to a pre-amp. A chopper1282 and lock-in amplifier 1290 setup enable low noise detection of thesample arm signal. The light in the reference arm 1287 passes through anempty container (cuvette, gas cell etc.) of the same kind as used in thesample arm. A substantially identical detector 1289, pre-amp and lock-inamplifier 1290 is used for detection of the reference arm signal. Thesignal may then be analyzed using a computer system 1291. This is oneparticular example of a method to remove fluctuations from the lightsource, but other components may be added and other configurations maybe used, and these are also intended to be covered by this disclosure.

Although particular examples of detection systems have been described,combinations of these systems or other systems may also be used, andthese are also within the scope of this disclosure. As one example,environmental fluctuations (such as turbulence or winds) may lead tofluctuations in the beam for active remote sensing or hyper-spectralimaging. A configuration such as FIG. 12D may be able to remove theeffect of environmental fluctuations. Yet another technique may be to“wobble” the light beam after the light source using a vibrating mirror.The motion may lead to the beam moving enough to wash out spatialfluctuations within the beam waist at the sample or detection system. Ifthe vibrating mirror is scanned faster than the integration time of thedetectors, then the spatial fluctuations in the beam may be integratedout. Alternately, some sort of synchronous detection system may be used,where the detection is synchronized to the vibrating frequency.

By use of an active illuminator, a number of advantages may be achieved,such as higher signal-to-noise ratios. For example, one way to improvethe signal-to-noise ratio would be to use modulation and lock-intechniques. In one embodiment, the light source may be modulated, andthen the detection system would be synchronized with the light source.In a particular embodiment, the techniques from lock-in detection may beused, where narrow band filtering around the modulation frequency may beused to reject noise outside the modulation frequency. In an alternateembodiment, change detection schemes may be used, where the detectionsystem captures the signal with the light source on and with the lightsource off. Again, for this system the light source may be modulated.Then, the signal with and without the light source is differenced. Thismay enable the sun light changes to be subtracted out. In addition,change detection may help to identify objects that change in the fieldof view. In the following some exemplary detection systems aredescribed.

In one embodiment, a SWIR camera or infrared camera system may be usedto capture the images. The camera may include one or more lenses on theinput, which may be adjustable. The focal plane assemblies may be madefrom mercury cadmium telluride material (HgCdTe), and the detectors mayalso include thermo-electric coolers. Alternately, the image sensors maybe made from indium gallium arsenide (InGaAs), and CMOS transistors maybe connected to each pixel of the InGaAs photodiode array. The cameramay interface wirelessly or with a cable (e.g., USB, Ethernet cable, orfiber optics cable) to a computer or tablet or smart phone, where theimages may be captured and processed. These are a few examples ofinfrared cameras, but other SWIR or infrared cameras may be used and areintended to be covered by this disclosure.

In another embodiment, an imaging spectrometer may be used to detect thelight received from the sample. For example, FIG. 14A shows a schematicdiagram 1400 of the basic elements of an imaging spectrometer. The inputlight 1401 from the sample may first be directed by a scanning mirrorand/or other optics 1402. An optical dispersing element 1403, such as agrating or prism, in the spectrometer may split the light into manynarrow, adjacent wavelength bands, which may then be passed throughimaging optics 1404 onto one or more detectors or detector arrays 1405.Some sensors may use multiple detector arrays to measure hundreds ofnarrow wavelength bands.

An example of a typical imaging spectrometer 1450 used in hyper-spectralimaging systems is illustrated in FIG. 14B. In this particularembodiment, the input light may be directed first by a tunable mirror1451. A front lens 1452 may be placed before the entrance slit 1453 andthe collector lens 1454. In this embodiment, the dispersing element is aholographic grating with a prism 1455, which separates the differentwavelength bands. Then, a camera lens 1456 may be used to image thewavelengths onto a detector or camera 1457.

FIGS. 14A and 14B provide particular examples, but some of the elementsmay not be used, or other elements may be added, and these are alsointended to be covered by this disclosure. For instance, a scanningspectrometer may be used before the detector, where a grating ordispersive element is scanned to vary the wavelength being measured bythe detector. In yet another embodiment, filters may be used before oneor more detectors to select the wavelengths or wavelength bands to bemeasured. This may be particularly useful if only a few bands orwavelengths are to be measured. The filters may be dielectric filters,Fabry-Perot filters, absorption or reflection filters, fiber gratings,or any other wavelength selective filter. In one embodiment, awavelength division multiplexer, WDM, may be used followed by one ormore detectors or detector arrays. One example of a planar wavelengthdivision multiplexer may be a waveguide grating router or an arrayedwaveguide grating. The WDM may be fiber coupled, and detectors may beplaced directly at the output or the detectors may be coupled throughfibers to the WDM. Some of these components may also be combined withthe configurations in FIGS. 14A and 14B.

One advantage of the SC lasers illustrated is that they may useall-fiber components, so that the SC laser can be all-fiber,monolithically integrated with no moving parts. The all-integratedconfiguration can consequently be robust and reliable.

The Figures provide examples of SC light sources that may advantageouslybe used for SWIR light generation in various medical and dentaldiagnostic and therapeutic applications. However, many other versions ofthe SC light sources may also be made that are intended to also becovered by this disclosure. For example, the SC generation fiber couldbe pumped by a mode-locked laser, a gain-switched semiconductor laser,an optically pumped semiconductor laser, a solid state laser, otherfiber lasers, or a combination of these types of lasers. Also, ratherthan using a fiber for SC generation, either a liquid or a gas cellmight be used as the nonlinear medium in which the spectrum is to bebroadened.

Even within the all-fiber versions illustrated such as in FIG. 9,different configurations could be used consistent with the disclosure.In an alternate embodiment, it may be desirous to have a lower costversion of the SWIR SC laser of FIG. 9. One way to lower the cost couldbe to use a single stage of optical amplification, rather than twostages, which may be feasible if lower output power is required or thegain fiber is optimized. For example, the pre-amplifier stage 902 mightbe removed, along with at least some of the mid-stage elements. In yetanother embodiment, the gain fiber could be double passed to emulate atwo stage amplifier. In this example, the pre-amplifier stage 902 mightbe removed, and perhaps also some of the mid-stage elements. A mirror orfiber grating reflector could be placed after the power amplifier stage906 that may preferentially reflect light near the wavelength of theseed laser 901. If the mirror or fiber grating reflector can transmitthe pump light near 940 nm, then this could also be used instead of thepump combiner 913 to bring in the pump light 912. The SC fiber 915 couldbe placed between the seed laser 901 and the power amplifier stage 906(SC is only generated after the second pass through the amplifier, sincethe power level may be sufficiently high at that time). In addition, anoutput coupler may be placed between the seed laser diode 901 and the SCfiber, which now may be in front of the power amplifier 906. In aparticular embodiment, the output coupler could be a power coupler ordivider, a dichroic coupler (e.g., passing seed laser wavelength butoutputting the SC wavelengths), or a wavelength division multiplexercoupler. This is just one further example, but a myriad of othercombinations of components and architectures could also be used for SClight sources to generate SWIR light that are intended to be covered bythis disclosure.

One definition of process analytical technology, PAT, is “a system fordesigning, analyzing and controlling manufacturing through timelyevaluations (i.e., during processing) of significant quality andperformance attributes of raw and in-process materials and processes,with the goal of ensuring final product quality.” Near-infrared or SWIRspectroscopy may have applications in the PAT of the pharmaceuticalindustry by providing, for example, quantitative analysis of multiplecomponents in a sample and in pack quantification of drugs informulation, as well as quality of a drug and quality control of complexexcipients used in formulation. The PAT process may benefit fromnear-infrared or SWIR spectroscopy for some steps, such as: raw materialidentification, active pharmaceutical ingredient applications, drying,granulation, blend uniformity and content uniformity. Some of thestrengths of near-infrared or SWIR spectroscopy include: radiation hasgood penetration properties, and, thus, minimal sample preparation maybe required; measurement results may be obtained rapidly, andsimultaneous measurements may be obtained for several parameters;non-destructive methods with little or no chemical waste; and organicchemicals that comprise most pharmaceutical products have unique spectrain the near-infrared and SWIR ranges, for example.

One goal of the manufacturing process and PAT may be the concept of a“smart” manufacturing process, which may be a system or manufacturingoperation responding to analytical data generated in real-time. Such asystem may also have an in-built “artificial intelligence” as decisionsmay be made whether to continue a manufacturing operation. For example,with respect to the raw materials, integration of the qualitymeasurement into smart manufacturing processes could be used to improvemanufacturing operations by ensuring that the correct materials of theappropriate quality are used in the manufacture. Similarly, a smartblender would be under software control and would respond to thereal-time spectral data collected.

FIG. 15 illustrates what might be an eventual flow-chart 1500 of a smartmanufacturing process. The manufacturing process 1501 may have as inputthe process feed 1502 and result in a process output 1503. A processcontroller 1504 may at least partially control the manufacturing process1501, and the controller 1504 may receive inputs from the closed loopcontrol (process parameters) 1505 as well as the on-line monitoring ofprocess parameters 1506. The feedback loops in the process could refinethe manufacturing process 1501 and improve the quality of the processoutput 1503. These are particular embodiments of the use ofnear-infrared or SWIR spectroscopy in the PAT of the pharmaceuticalindustry, but other variations, combinations, and methods may also beused and are intended to be covered by this disclosure.

The discussion thus far has centered on use of near-infrared or SWIRspectroscopy in applications such as identification of counterfeitdrugs, detection of illicit drugs, and pharmaceutical process control.Although drugs and pharmaceuticals are one example, many other fieldsand applications may also benefit from the use of near infrared or SWIRspectroscopy, and these may also be implemented without departing fromthe scope of this disclosure. As just another example, near-infrared orSWIR spectroscopy may also be used as an analytic tool for food qualityand safety control. Applications in food safety and quality assessmentinclude contaminant detection, defect identification, constituentanalysis, and quality evaluation. The techniques described in thisdisclosure are particularly valuable when non-destructive testing isdesired at stand-off or remote distances.

Wireless Link to the Cloud

The non-invasive dental caries measurement device may also benefit fromcommunicating the data output to the “cloud” (e.g., data servers andprocessors in the web remotely connected) via wireless means. Thenon-invasive devices may be part of a series of biosensors applied tothe patient, and collectively these devices form what might be called abody area network or a personal area network. The biosensors andnon-invasive devices may communicate to a smart phone, tablet, personaldata assistant, computer and/or other microprocessor-based device, whichmay in turn wirelessly or over wire and/or fiber optic transmit some orall of the signal or processed data to the internet or cloud. The cloudor internet may in turn send the data to dentists, doctors or healthcare providers as well as the patients themselves. Thus, it may bepossible to have a panoramic, high-definition, relatively comprehensiveview of a patient that doctors and dentists can use to assess and managedisease, and that patients can use to help maintain their health anddirect their own care.

In a particular embodiment 1300, the non-invasive measurement device1301 may comprise a transmitter 1303 to communicate over a firstcommunication link 1304 in the body area network or personal areanetwork to a receiver in a smart phone, tablet, cell phone, PDA, and/orcomputer 1305, for example. For the measurement device 1301, it may alsobe advantageous to have a processor 1302 to process some of the measureddata, since with processing the amount of data to transmit may be less(hence, more energy efficient). The first communication link 1304 mayoperate through the use of one of many wireless technologies such asBluetooth, Zigbee, WiFi, IrDA (infrared data association), wireless USB,or Z-wave, to name a few. Alternatively, the communication link 1304 mayoccur in the wireless medical band between 2360 MHz and 2390 MHz, whichthe FCC allocated for medical body area network devices, or in otherdesignated medical device or WMTS bands. These are examples of devicesthat can be used in the body area network and surroundings, but otherdevices could also be used and are included in the scope of thisdisclosure.

The personal device 1305 may store, process, display, and transmit someof the data from the measurement device 1301. The device 1305 maycomprise a receiver, transmitter, display, voice control and speakers,and one or more control buttons or knobs and a touch screen. Examples ofthe device 1305 include smart phones such as the Apple iPhones® orphones operating on the Android or Microsoft systems. In one embodiment,the device 1305 may have an application, software program, or firmwareto receive and process the data from the measurement device 1301. Thedevice 1305 may then transmit some or all of the data or the processeddata over a second communication link 1306 to the internet or “cloud”1307. The second communication link 1306 may advantageously comprise atleast one segment of a wireless transmission link, which may operateusing WiFi or the cellular network. The second communication link 1306may additionally comprise lengths of fiber optic and/or communicationover copper wires or cables.

The internet or cloud 1307 may add value to the measurement device 1301by providing services that augment the measured data collected. In aparticular embodiment, some of the functions performed by the cloudinclude: (a) receive at least a fraction of the data from the device1305; (b) buffer or store the data received; (c) process the data usingsoftware stored on the cloud; (d) store the resulting processed data;and (e) transmit some or all of the data either upon request or based onan alarm. As an example, the data or processed data may be transmitted1308 back to the originator (e.g., patient or user), it may betransmitted 1309 to a health care provider or doctor or dentist, or itmay be transmitted 1310 to other designated recipients.

Service providers coupled to the cloud 1307 may provide a number ofvalue-add services. For example, the cloud application may store andprocess the dental data for future reference or during a visit with thedentist or healthcare provider. If a patient has some sort of medicalmishap or emergency, the physician can obtain the history of the dentalor physiological parameters over a specified period of time. In anotherembodiment, alarms, warnings or reminders may be delivered to the user1308, the healthcare provider 1309, or other designated recipients 1310.These are just some of the features that may be offered, but many othersmay be possible and are intended to be covered by this disclosure. As anexample, the device 1305 may also have a GPS sensor, so the cloud 1307may be able to provide time, date, and position along with the dental orphysiological parameters. Thus, if there is a medical or dentalemergency, the cloud 1307 could provide the location of the patient tothe dental or healthcare provider 1309 or other designated recipients1310. Moreover, the digitized data in the cloud 1307 may help to movetoward what is often called “personalized medicine.” Based on the dentalor physiological parameter data history, medication or medical/dentaltherapies may be prescribed that are customized to the particularpatient. Another advantage for commercial entities may be that byleveraging the advances in wireless connectivity and the widespread useof handheld devices such as smart phones that can wirelessly connect tothe cloud, businesses can build a recurring cost business model evenusing non-invasive measurement devices.

Beyond the above benefits, the cloud application 1307 and application onthe device 1305 may also have financial value for companies developingdevices 1301 such as a non-invasive blood constituent monitor. In thecase of glucose monitors, the companies make the majority of theirrevenue on the measurement strips. However, with a non-invasive monitor,there is no need for strips, so there is less of an opportunity forrecurring costs (e.g., the razor/razor blade model does not work fornon-invasive devices). On the other hand, people may be willing to pay aperiodic fee for the value-add services provided on the cloud 1307.Diabetic patients, for example, would probably be willing to pay aperiodic fee for monitoring their glucose levels, storing the history ofthe glucose levels, and having alarm warnings when the glucose levelfalls out of range. Similarly, patients taking ketone bodies supplementfor treatment of disorders characterized by impaired glucose metabolism(e.g., Alzheimer's, Parkinson's, Huntington's or ALS) may need tomonitor their ketone bodies level. These patients would also probably bewilling to pay a periodic fee for the value-add services provided on thecloud 1307. Thus, by leveraging the advances in wireless connectivityand the widespread use of handheld devices such as smart phones that canwirelessly connect to the cloud, businesses can build a recurring costbusiness model even using non-invasive measurement devices.

In addition, it may be advantageous to use pattern matching algorithmsand other software and mathematical methods to identify the bloodconstituents of interest. In one embodiment, the spectrum may becorrelated with a library of known spectra to determine the overlapintegrals, and a threshold function may be used to quantify theconcentration of different constituents. This is just one way to performthe signal processing, and many other techniques, algorithms, andsoftware may be used and would fall within the scope of this disclosure.

One of the issues in measuring a particular blood constituent is theinterfering and overlapping signal from other blood constituents. Theselection of the constituent of interest may be improved using a numberof techniques. For example, a higher light level or intensity mayimprove the signal-to-noise ratio for the measurement. Second,mathematical modeling and signal processing methodologies may help toreduce the interference, such as multivariate techniques, multiplelinear regression, and factor-based algorithms, for example. Forinstance, a number of mathematical approaches include multiple linearregression, partial least squares, and principal component regression(PCR). Also, various mathematical derivatives, including the first andsecond derivatives, may help to accentuate differences between spectra.In addition, by using a wider wavelength range and using more samplingwavelengths may improve the ability to discriminate one signal fromanother.

Described herein are just some examples of the beneficial use ofnear-infrared or SWIR lasers for non-invasive measurements of dentalcaries and early detection of carious regions. However, many otherdental or medical procedures can use the near-infrared or SWIR lightconsistent with this disclosure and are intended to be covered by thedisclosure.

Although the present disclosure has been described in severalembodiments, a myriad of changes, variations, alterations,transformations, and modifications may be suggested to one skilled inthe art, and it is intended that the present disclosure encompass suchchanges, variations, alterations, transformations, and modifications asfalling within the spirit and scope of the appended claims.

While exemplary embodiments are described above, it is not intended thatthese embodiments describe all possible forms of the disclosure. Rather,the words used in the specification are words of description rather thanlimitation, and it is understood that various changes may be madewithout departing from the spirit and scope of the disclosure.Additionally, the features of various implementing embodiments may becombined to form further embodiments of the disclosure. While variousembodiments may have been described as providing advantages or beingpreferred over other embodiments with respect to one or more desiredcharacteristics, as one skilled in the art is aware, one or morecharacteristics may be compromised to achieve desired system attributes,which depend on the specific application and implementation. Theseattributes include, but are not limited to: cost, strength, durability,life cycle cost, marketability, appearance, packaging, size,serviceability, weight, manufacturability, ease of assembly, etc. Theembodiments described herein that are described as less desirable thanother embodiments or prior art implementations with respect to one ormore characteristics are not outside the scope of the disclosure and maybe desirable for particular applications.

What is claimed is:
 1. A measurement system comprising: a light sourcecomprising a plurality of semiconductor sources that are configured togenerate an output optical beam with one or more optical wavelengths,the light source configured to increase signal-to-noise ratio byincreasing a light intensity relative to an initial light intensity fromat least one of the plurality of semiconductor sources; a measurementdevice configured to: receive a portion of the output optical beam, anddeliver an analysis output beam to a sample; a receiver configured to:receive and process at least a portion of the analysis output beamreflected or transmitted from the sample, generate an output signalrepresenting at least in part a non-invasive measurement on bloodcontained within the sample, synchronize to the light source, capturelight while the semiconductor sources are off and convert the capturedlight into a first signal, capture light while at least one of thesemiconductor sources is on and convert the captured light into a secondsignal, the captured light including at least a part of the at least aportion of the analysis output beam reflected or transmitted from thesample, and the measurement system further configured to improve thesignal-to-noise ratio by differencing the first signal and the secondsignal; a smart phone or tablet comprising a wireless receiver, awireless transmitter, a display, a microphone, a speaker, one or morebuttons or knobs, a microprocessor and a touch screen, the smart phoneor tablet configured to: receive and process at least a portion of theoutput signal, store and display the processed output signal, andtransmit at least a portion of the processed output signal over awireless transmission link; and a cloud configured to: receive, over thewireless transmission link, an output status comprising the at least aportion of the processed output signal, process the received outputstatus to generate processed data, and store the processed data.
 2. Themeasurement system of claim 1, wherein the plurality of semiconductorsources comprises at least one of: light emitting diodes (LEDs), laserdiodes (LD's), tunable LD's, and super-luminescent laser diodes (SLDs),and wherein the measurement system further comprises a reflectivesurface to receive and redirect at least some of the at least a portionof the analysis output beam reflected or transmitted from the sample. 3.The measurement system of claim 1, wherein the light source is furtherconfigured to increase the light intensity from the plurality ofsemiconductor sources by spatially coupling the optical output beam fromat least two of the plurality of semiconductor sources.
 4. Themeasurement system of claim 1, wherein the receiver comprises aplurality of detectors arranged along a first arc, and wherein theplurality of semiconductor sources are arranged along a second arc. 5.The measurement system of claim 4, wherein the first arc is offset fromthe second arc.
 6. The measurement system of claim 4, wherein the firstarc and the second arc are concentric.
 7. The measurement system ofclaim 6, wherein the plurality of semiconductor sources comprises sixlight emitting diodes, and wherein the receiver comprises six detectors.8. The measurement system of claim 7, wherein the six detectors arelocated on the first arc surrounding the six light emitting diodes. 9.The measurement system of claim 8, wherein the measurement system isconfigured to use artificial intelligence in making decisions; whereinthe measurement system is configured to perform pattern identificationor classification, and wherein the measurement system is configured toapply a threshold function to a comparison with a stored data set; andwherein the measurement system is at least in part configured forselection or identification of an object, and wherein the measurementsystem is configured to improve a signal-to-noise ratio of the selectionor identification by applying regression signal processing methodologiesor multivariate techniques.
 10. The measurement system of claim 8,wherein the light source is configured to further increasesignal-to-noise ratio by increasing a pulse rate of at least one of theplurality of semiconductor sources from an initial non-zero pulse rate.11. A measurement system comprising: a wearable measurement device formeasuring one or more physiological parameters, including a light sourcecomprising a plurality of semiconductor sources that are configured togenerate an output optical beam with one or more optical wavelengths;the light source configured to increase signal-to-noise ratio byincreasing a light intensity relative to an initial light intensity fromat least one of the plurality of semiconductor sources; the wearablemeasurement device configured to receive a portion of the output opticalbeam and to deliver an analysis output beam to a sample; the wearablemeasurement device further comprising a receiver configured to: receiveand process at least a portion of the analysis output beam reflected ortransmitted from the sample, generate an output signal representing atleast in part a non-invasive measurement on blood contained within thesample, synchronize to the light source, capture light while thesemiconductor sources are off and convert the captured light into afirst signal, capture light while at least one of the semiconductorsources is on and convert the captured light into a second signal, thecaptured light including at least a part of the at least a portion ofthe analysis output beam reflected or transmitted from the sample,wherein the measurement system is further configured to improve thesignal-to-noise ratio by differencing the first signal and the secondsignal; a smart phone or tablet comprising a wireless receiver, awireless transmitter, a display, a microphone, a speaker, one or morebuttons or knobs, a microprocessor and a touch screen, the smart phoneor tablet configured to receive and process at least a portion of theoutput signal, to store and display the processed output signal, and totransmit a portion of the processed output signal over a wirelesstransmission link; and a cloud configured to receive over the wirelesstransmission link an output status comprising the at least a portion ofthe processed output signal, to process the received output status togenerate processed data and to store the processed data, and wherein thecloud is capable of storing a history of at least a portion of thereceived output status over a specified period of time.
 12. Themeasurement system of claim 11, wherein the measurement system isconfigured to use artificial intelligence in making decisions; whereinthe measurement system is configured to perform pattern identificationor classification, and wherein the measurement system is configured toapply a threshold function to a comparison with a stored data set; andwherein the measurement system is at least in part configured forselection or identification of an object, and wherein the measurementsystem is configured to improve a signal-to-noise ratio of the selectionor identification by applying regression signal processing methodologiesor multivariate techniques.
 13. The measurement system of claim 12,wherein the light source is configured to further increase thesignal-to-noise ratio by increasing a pulse rate of at least one of theplurality of semiconductor sources from an initial non-zero pulse rate.14. The measurement system of claim 11, wherein the plurality ofsemiconductor sources comprises at least one of: light emitting diodes(LEDs), laser diodes (LD's), tunable LD's, and super-luminescent laserdiodes (SLDs), and the measurement system further comprising areflective surface to receive and redirect at least some of the at leasta portion of the analysis output beam reflected or transmitted from thesample.
 15. The measurement system of claim 11, wherein the receivercomprises a plurality of detectors arranged along a first arc, andwherein the plurality of semiconductor sources are arranged along asecond arc that is offset from the first arc.
 16. The measurement systemof claim 15, wherein the first arc and the second arc are concentric.17. The measurement system of claim 16, wherein the plurality ofsemiconductor sources comprises six light emitting diodes, and whereinthe receiver comprises six detectors.
 18. The measurement system ofclaim 17, wherein the six detectors are located on the first arcsurrounding the six light emitting diodes.
 19. A wearable device for usewith a smart phone or tablet, the wearable device comprising: ameasurement device including a light source comprising a plurality ofsemiconductor sources for measuring one or more physiologicalparameters, the measurement device configured to: generate, bymodulating at least one of the semiconductor sources having an initiallight intensity, an input optical beam having one or more opticalwavelengths, and receive and to deliver a portion of the input opticalbeam to tissue, wherein the tissue reflects at least a portion of theinput optical beam delivered to the tissue; the measurement devicefurther comprising a receiver configured to: capture light while thesemiconductor sources are off and convert the captured light into afirst signal, and capture light while at least one of the semiconductorsources is on and convert the captured light into a second signal, thecaptured light including at least a portion of the input optical beamreflected from the tissue; synchronize to the modulation of the at leastone of the semiconductor sources; the measurement device furtherconfigured to improve a signal-to-noise ratio of the input optical beamreflected from the tissue by: differencing the first signal and thesecond signal, and increasing the light intensity relative to theinitial light intensity from at least one of the semiconductor sources;the measurement device further configured to generate an output signalrepresenting at least in part a non-invasive measurement on bloodcontained within the tissue; the wearable device configured tocommunicate with the smart phone or tablet, the smart phone or tabletcomprising a wireless receiver, a wireless transmitter, a display, avoice input module, a speaker, and a touch screen; and the smart phoneor tablet configured to: receive and to process at least a portion ofthe output signal, store and display the processed output signal, andtransmit at least a portion of the processed output signal over awireless transmission link.
 20. The wearable device of claim 19, whereinthe light source is configured to further improve the signal-to-noiseratio of the input optical beam reflected from the tissue by increasinga pulse rate of at least one of the plurality of semiconductor sourcesfrom an initial non-zero pulse rate.
 21. The wearable device of claim20, wherein the receiver comprises a plurality of detectors arrangedalong a first arc, and wherein the plurality of semiconductor sourcesare arranged along a second arc that is offset from the first arc. 22.The wearable device of claim 21, wherein the first arc and the secondarc are concentric.
 23. The wearable device of claim 22, wherein theplurality of semiconductor sources comprises six light emitting diodes,and wherein the receiver comprises six detectors.
 24. The wearabledevice of claim 23, wherein the six detectors are located on the firstarc surrounding the six light emitting diodes.
 25. The wearable deviceof claim 19, further comprising a cloud configured to: receive, over thewireless transmission link, an output status comprising the at least aportion of the processed output signal, process the output status togenerate processed data, and store the processed data, and wherein thecloud is capable of storing a history of at least a portion of theoutput status over a specified period of time.
 26. The wearable deviceof claim 19, wherein the wearable device is configured to use artificialintelligence in making decisions; wherein the wearable device isconfigured to perform pattern identification or classification, andwherein the wearable device is configured to apply a threshold functionto a comparison with a stored data set; and wherein the wearable deviceis at least in part configured for selection or identification of anobject, and wherein the wearable device is configured to improve asignal-to-noise ratio of the selection or identification by applyingregression signal processing methodologies or multivariate techniques.27. The wearable device of claim 19, wherein the measurement devicefurther comprises a reflective surface configured to receive andredirect at least a portion of light reflected from the tissue.